The preparation of substituted 1(2H)-isoquinolinones from polylithiated 2-(2-methylphenyl)hydrazinecarboxylic acid esters

Synthetic Communications

Volumn 26, Issue 9, 1996, Pages 1763-1774

  Koller, Madlene U ^a   Church, A Cameron ^a   Griffith, Cynthia L ^a   Hines, Margaret A ^a   Lachicotte, Rene J ^a   Taylor, Richard A ^a   Beam, Charles F ^a  

^a School of Business   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ISOQUINOLINE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0029948732     PISSN: 00397911     EISSN: None     Source Type: Journal    
DOI: 10.1080/00397919608002616     Document Type: Article

References (53)

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8. (b) Bailey, D.M. and DeGarzia, Tetrahedron Lett., 1970, 9, 633.
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11. (b) Shamma, M., and Mionot, J.L., "Isoquinoline Alkaloid Research", Plenum Press, New York, New York, 1978, p. 51;
12. (c) Iida, H., Kawano, K., Kikuchi, T., and Yoshimizu, Yakuggaka Zasshi, 1976, 96, 176.
13. (d) Girling, I.R., and Widdowson, D.A., J. Chem. Soc., Perkin Trans 1, 1988, 1317.
14. (e) VanderGoot., H., and Nauta, W., Th., Acta Pharm. Suecica, 1971, 8, 373.
15. (f) Izumi, T. and Marishita, N., J. Heterocycl. Chem, 1994, 31, 145.
16. (g) Cobas, A., Guitian, E., and Castedo, L., J. Org. Chem., 1993, 58, 3113.
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19. (j) Stanoeva, E., Haimova, M., and Ognyanov, V., Liebigs Ann., Chem., 1984, 389.
20. 2-Acylamino-3-phenyl-1(2H)-isoquinolinones: Ueno, S., Sugihara, K., Hirayama, H., and Ichino, M., Japan Kokai, 1976, 76,122,075; Chem. Abstr., 1977, 87, 5822a.
21. 2-Acylamino-3-phenyl-1(2H)-isoquinolinones: Ueno, S., Sugihara, K., Hirayama, H., and Ichino, M., Japan Kokai, 1976, 76,122,075; Chem. Abstr., 1977, 87, 5822a.
22. 2-Amaino-1(2H)-isoquinolinones: (a) Huisgen, R. and Rauenbusch, E., Ann., 1961, 641, 51. (b) Boyers, J.T. and Glover, E.E., J. Chem. Soc., Perkin Trans. 1, 1977, 1960. (c) Datta. D., and Usgaonkae, Indian J. Chem., 1981, 20B, 376. (d) Gurevich, A.I., Kolasov, M.N., Omelchenko, V.N., Onoprienko,V.V., and Petrenko, G.I., Bioorg. Khim., 1975, 1, 166. (e) Legrand, L. and Lozac'h, Bull. Soc. Chem. Fr., 1970, 2240.
23. 2-Amaino-1(2H)-isoquinolinones: (a) Huisgen, R. and Rauenbusch, E., Ann., 1961, 641, 51. (b) Boyers, J.T. and Glover, E.E., J. Chem. Soc., Perkin Trans. 1, 1977, 1960. (c) Datta. D., and Usgaonkae, Indian J. Chem., 1981, 20B, 376. (d) Gurevich, A.I., Kolasov, M.N., Omelchenko, V.N., Onoprienko,V.V., and Petrenko, G.I., Bioorg. Khim., 1975, 1, 166. (e) Legrand, L. and Lozac'h, Bull. Soc. Chem. Fr., 1970, 2240.
24. 2-Amaino-1(2H)-isoquinolinones: (a) Huisgen, R. and Rauenbusch, E., Ann., 1961, 641, 51. (b) Boyers, J.T. and Glover, E.E., J. Chem. Soc., Perkin Trans. 1, 1977, 1960. (c) Datta. D., and Usgaonkae, Indian J. Chem., 1981, 20B, 376. (d) Gurevich, A.I., Kolasov, M.N., Omelchenko, V.N., Onoprienko,V.V., and Petrenko, G.I., Bioorg. Khim., 1975, 1, 166. (e) Legrand, L. and Lozac'h, Bull. Soc. Chem. Fr., 1970, 2240.
25. 2-Amaino-1(2H)-isoquinolinones: (a) Huisgen, R. and Rauenbusch, E., Ann., 1961, 641, 51. (b) Boyers, J.T. and Glover, E.E., J. Chem. Soc., Perkin Trans. 1, 1977, 1960. (c) Datta. D., and Usgaonkae, Indian J. Chem., 1981, 20B, 376. (d) Gurevich, A.I., Kolasov, M.N., Omelchenko, V.N., Onoprienko,V.V., and Petrenko, G.I., Bioorg. Khim., 1975, 1, 166. (e) Legrand, L. and Lozac'h, Bull. Soc. Chem. Fr., 1970, 2240.
26. 2-Amaino-1(2H)-isoquinolinones: (a) Huisgen, R. and Rauenbusch, E., Ann., 1961, 641, 51. (b) Boyers, J.T. and Glover, E.E., J. Chem. Soc., Perkin Trans. 1, 1977, 1960. (c) Datta. D., and Usgaonkae, Indian J. Chem., 1981, 20B, 376. (d) Gurevich, A.I., Kolasov, M.N., Omelchenko, V.N., Onoprienko,V.V., and Petrenko, G.I., Bioorg. Khim., 1975, 1, 166. (e) Legrand, L. and Lozac'h, Bull. Soc. Chem. Fr., 1970, 2240.
27. Only the ethyl 2-(3-methylphenyl)hydrazinecarboxylate and 2-(4-methylphenyl)hydrazinecrboxylate isomers have been reported. See: Grekov, A.P. and Veselov, V. A., Zh. Org. Khim., 1971, 7, 323; Chem. Abstr., 1971, 75, 48108s.
28. Only the ethyl 2-(3-methylphenyl)hydrazinecarboxylate and 2-(4-methylphenyl)hydrazinecrboxylate isomers have been reported. See: Grekov, A.P. and Veselov, V. A., Zh. Org. Khim., 1971, 7, 323; Chem. Abstr., 1971, 75, 48108s.
29. (a) We found Schotten-Baumann condensation procedures of aromatic carboxylic acid chlorides too general. In order to avoid excess diacylation and still be able to make the entry compound expediently, we used a procedure that gave the desired entry compounds in 50 - 70% yield.
30. (b) See also: Carpino, L.A., Terry, P.H., and Crowley, P.J., J. Org. Chem., 1961, 26, 4336.
31. (a) Fulmer, T.D., Dasher, L.P., Bobb, B.L., Wilson, J.D., Sides, K.L., and Beam, C.F., J. Heterocycl. Chem., 1980, 17, 799.
32. (b) Huff, A.M., Hall, H.L., Smith, M.J., O'Grady, S.A., Waters, F.C., Fengl, R.W., Welch, J.A., and Beam, C.F., J. Heterocycl. Chem., 1985, 22, 501.
33. (c) Duncan, D. C., Trumbo, T.A., Almquist, C.D., Lentz, T.A., and Beam, C.F., J. Heterocycl. Chem., 1987, 24, 555.
34. 3). The spectra indicated that metalation of the ortho methyl hydrogens had not occurred.
35. 3), 2.43 (s, ArH) and 7.12 - 7.68 (m, ArH).
36. Microanalysis for C, H, and N were performed by Quantitative Technologies, Inc., P.O. Box 470, Salem Industrial Park, Bldg. 5, Whitehouse, NJ 08888 and Robertsons Laboratory, 8 Samson Avenue, Madison, NJ 07940. [Compd. No. from Table] Calcd. for 1: C, 66.66; H, 4.97; N, 8.64. Found: C, 66.90; H, 5.13; N, 8.37. Calcd. for 2: C, 65.80; H, 4.55; N, 9.03. Found: C, 65.74; H, 4.80; N, 8.74. Calcd. for 3: C, 68.17; H, 5.72; N, 7.95. Found: C, 68.16; H, 5.79; N, 7.96 Calcd. for 4: C, 70.79; H, 5.63; N, 8.69. Found: C, 70.49; H, 5.65; N, 8.65. Calcd. for 5: C, 72.51; H, 6.64; N, 7.69. Found: C, 72.54; H, 6.50; N, 7.69. Calcd. for 6: C, 71.41; H, 5.99; N, 8.33. Found: C, 71.40; H, 6.05; H, 8.25. Calcd. for 7: C, 71.98; H, 6.33; N, 7.99. Found: C, 72.04; H, 6.47; N, 7.88. Calcd. for 8: C, 64.78; H, 5.16; N, 7.55. Found: C, 664.93; H, 5.13; N, 7.58. Calcd. for 9: C, 63.07; H, 4.41; N, 8.17. Found: C, 63.15; H, 4.55; N, 8.07. Calcd. for 10: C, 68.84; H, 6.05; N, 7.64. Found: C, 68.88; H, 6.09; N, 7.56. Calcd. for 11: C, 63.31; H, 5.57; N, 7.03. Found: C, 63.22; H, 5.74; N, 6.88. Calcd. for 12: C, 64.78; H, 6.14; N, 6.57. Found: C, 64.69; H, 6.21; N, 6.66. Calcd. for 13: C, 65.38; H, 5.16; N, 8.96, Found: C, 65.34; H, 5.28; N, 8.85. Calcd. for 14: C, 57.69; H, 5.81; N, 13.45. Found: C, 57.77; H, 5.86; N, 13.49. Calcd. for 15: C, 59.45; H, 6.35; N, 12.60. Found: C, 59.38; H, 6.44; N, 12.46. Calcd. for 16: C, 62.38; H, 7.25; N, 11.19. Found: C, 62.43; H, 6.99; N, 11.19.
37. Brown, J., Sides, K.L., Fulmer, T.D., and Beam, C.F., J. Heterocycl. Chem., 1979, 16, 1669.
38. Mack, H.M., Davis, E.A., Kadkhodayan, B., Taylor, R.A., Duncan, D.C., and Beam, C.F., J. Heterocycl. Chem., 1987, 24, 1733.
39. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
40. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
41. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
42. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
43. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
44. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
45. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
46. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
47. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
48. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
49. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
50. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
51. There are numerous reports concerning the preparation of 2,3-benzodiazepin-1-ones, and in each case the double bond is between N-3 and C-4, and not between C-4 and C-5. The latter location of the double bond would be in the 2,3-benzodiazepin-1-ones, if formed during the cyclization, prior to rearrangement to the 1 (2H)-isoquinolinone (a) Ames, D.A., and Dodds, J. Chem. Soc., Perkin Trans. 1, 1972, 705; (b) Wolbling, H., Ber., 1905, 38, 3846. (c) Wolbling, H., Ber., 1905, 2845. (d) Flammang, M., C.R. Hebd. Seances Acad. Sci. Ser. C, 1978, 286, 671; Chem. Abstr., 1978, 89, 146878b. (e) Flammang, M., and Wermuth, C.G., Eur. J. Med. Chem.-Chim. Ther., 1977, 12, 121. (f) Flammang, M. and Wermuth, C.G., C.R. Hebd. Seances Acad. Sci. Ser. C, 1980, 290, 361; Chem. Abstr., 1980, 93, 203556d. (g) Rose, A., and Buu-Hoi, N.P., J. Chem. Soc., 1968, C, 2205. (h) Vorozhtov, N.N., and Petuchkova, A.T., J. Gen Chem. USSR (Engl. Trans.), 1957, 27, 2342. (i) Somei, M., Karasawa, Y., Shoda, T., and Kaneko, C., Chem. Pharm. Bull., Japan., 1981, 29, 249. (j) Grogan, F., O'Brian, A.E., Philbin, E.M., O'Conner, N.S., Tommoney, R.F., and Wheeler, T.S., Tetrahedron, 1958, 3, 140. (k) Legrand, L. and Lozac'h, N., Bull. Soc. Chim. Fr., 1970, 2237 and 2240.
52. Initially 95% ethanol was used. If crystals did not form in several hours or overnight (refrigerator), a few drops of water or a few ice crystals were added.
53. A 1.6 M solution in hexanes was obtained from Aldrich Chemical Co. This material is satisfactory enough to effect metalation and dilute enough to permit expedient and safe handling.