A short and efficient synthesis of zamifenacin a muscarinic M3 receptor antagonist

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 10, 1997, Pages 1343-1344

  Cossy, Janine ^a   Dumas, Cécile ^a   Pardo, Domingo Gomez ^a  

^a CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

MUSCARINIC M3 RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG; ZAMIFENACIN;

ARTICLE; DRUG SYNTHESIS; IN VITRO STUDY; INFRARED SPECTROPHOTOMETRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS;

EID: 0031579963     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00221-7     Document Type: Article

References (13)

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2. Alker, D.; Cross, P.E.; Wallis, R.M. (Pfizer Ltd., Pfizer Inc.) Eur. Pat. Appl. EP 350 309, 1990, Chem. Abstr. 1990, 112, 235186k.
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9. +•, 0.1), 218 (8), 149 (13), 135 (4), 114 (100).
10. Cossy J., Dumas C., Michel P., Gomez Pardo D. Tetrahedron Lett. 36:1995;549-552.
11. (-)-5: [α]D20 = -1 (c = 0.68, EtOH). IR (NaCl) ν: 3360, 1505, 1445, 1250 cm-1. NMR 1H (300 MHz, CDCl3) δ: 1.41-1.85 (m, 3H), 1.91-2.08 (m, 1H), 2.72-3.04 (m, 8H), 3.98 (m, 1H), 5.88 (s, 2H), 6.60-6.75 (m, 3H). NMR 13C (75 MHz, CDCl3) δ: 21.8 (CH2), 31.9 (CH2), 33.1 (CH2), 53.5 (CH2), 60.4 (2CH2), 66.2 (CH), 100.7 (CH2), 108.1 (CH), 109.0 (CH), 121.3 (CH), 134.0 (C), 145.7 (C), 147.5 (C). MS (EI, 70 eV) m/z: 249 (M+•, 1), 232 (2), 210 (100), 135 (4), 96 (16).
12. Zamifenacin: [α]D20 = +20 (c = 0.26, EtOH), [ : [α]D20 = +22.5 (c = 1.5, EtOH)]. IR (NaCl): 1505, 1490, 1250 cm-1. NMR 1H (300 MHz, CDCl3) δ: 1.29-1.58 (m, 3H), 1.74-1.80 (m, 1H), 1.98-2.14 (m, 2H), 2.55-2.61 (m, 2H), 2.69-2.73 (m, 2H), 2.81 (dd, 2J=11.0 Hz, 3J=1.1 Hz, 1H), 3.11 (dd, 2J=10.5 Hz, 3J=3.9 Hz, 1H), 3.54-3.63 (m, 1H), 5.58 (s, 1H), 5.94 (s, 2H), 6.63-6.76 (m, 3H), 7.26-7.37 (m, 10H). NMR 13C (75 MHz, CDCl3) δ: 23.4 (CH2), 30.7 (CH2), 33.1 (CH2), 53.3 (CH2), 58.6 (CH2), 60.7 (CH2), 64.2 (CH), 79.9 (CH), 100.7 (CH2), 108.1 (CH), 109.1 (CH), 121.4 (CH), 127.1 (CH), 127.4 (CH), 128.0 (2CH), 128.2 (2CH), 128.3 (2CH), 128.4 (2CH), 134.1 (C), 141.0 (C), 142.6 (C), 145.7 (C), 147.5 (C). MS (EI, 70 /z: 415 (M+•, 0.1), 280 (4), 168 (14), 167 (100), 165 (8), 152 (5).
13. We have previously shown that the ring enlargement occurs with no racemization, see .