Acetic Acid → N-{(3aS*,4S*,6aR*)-2-[6,6-bis(4-fluorophenyl)hexyl]octahydrocyclopenta[c]pyrrol-4-yl}-N-cyclopropyl-3-(trifluoromethyl)benzenesulfonamide

HRID 2363530ノート

反応式

HRID 2363530 の反応式
[CH:1]1([N:4]([C@@H:18]2[C@H:25]3[C@H:21]([CH2:22][NH:23][CH2:24]3)[CH2:20][CH2:19]2)[S:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)(=[O:7])=[O:6])[CH2:3][CH2:2]1.[F:26][C:27]1[CH:32]=[CH:31][C:30]([CH:33]([C:40]2[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=2)[CH2:34][CH2:35][CH2:36][CH2:37][CH:38]=O)=[CH:29][CH:28]=1.C(O)(=O)C.C([BH3-])#N>ClCCl>[F:26][C:27]1[CH:28]=[CH:29][C:30]([CH:33]([C:40]2[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=2)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][N:23]2[CH2:24][C@H:25]3[C@@H:18]([N:4]([CH:1]4[CH2:2][CH2:3]4)[S:5]([C:8]4[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:17])[F:16])[CH:9]=4)(=[O:6])=[O:7])[CH2:19][CH2:20][C@H:21]3[CH2:22]2)=[CH:31][CH:32]=1

参加物

6

反応物 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 66590637N-cyclopropyl-N-[(3aS*,4S*,6aR*)-octahydrocyclopenta[c]pyrrol-4-yl]-3-(trifluoromethyl)benzenesulfonamideHCID 866419776,6-Bis(4-fluorophenyl)hexanal

生成物 1

HCID 68416645N-{(3aS*,4S*,6aR*)-2-[6,6-bis(4-fluorophenyl)hexyl]octahydrocyclopenta[c]pyrrol-4-yl}-N-cyclopropyl-3-(trifluoromethyl)benzenesulfonamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

N-Cyclopropyl-N-[(3aS*,4S*,6aR*)-octahydrocyclopenta[c]pyrrol-4-yl]-3-(trifluoromethyl)benzenesulfonamide from Example 201 (140 mg, 0.374 mmol) and 6,6-bis(4-fluorophenyl)hexanal (108 mg, 0.374 mmol) were combined in dichloromethane (2 mL) and then acetic acid (1 mL) was added. The reaction was stirred at room temperature for 20 minutes, then PS-cyanoborohydride (306 mg, 0.748 mmol) was added. The reaction mixture was stirred at room temperature overnight, then filtered and the resin washed with dichloromethane. The solvent was removed in vacuo and the crude material purified using a silica gel cartridge (Analogix®, Burlington, Wis., RS-12) eluting with 1-10% methanol (2 N ammonia)/dichloromethane to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.50 (s, 1H), 8.36 (d, J=7.9, 1H), 7.95 (d, J=7.9, 1H), 7.76 (dd, J=6.4, 14.2, 1H), 7.33 (dd, J=5.6, 8.3, 4H), 7.18-7.11 (m, 4H), 3.96 (dd, J=8.0, 16.3, 2H), 3.18-3.10 (m, 1H), 2.82 (dd, J=3.5, 9.5, 1H), 2.50-2.44 (m, 2H), 2.39 (t, J=8.0, 1H), 2.31-2.21 (m, 4H), 2.03 (dd, J=7.8, 15.3, 2H), 1.91 (dt, J=3.5, 10.4, 1H), 1.59 (dt, J=5.6, 11.5, 1H), 1.51 (dd, J=10.6, 16.2, 1H), 1.46-1.33 (m, 6H), 1.28 (dd, J=7.4, 15.1, 2H), 1.08 (td, J=5.0, 10.5, 1H), 0.84 (dt, J=6.9, 12.6, 1H), 0.75-0.66 (m, 1H); MS (ESI+) m/z 647 (M+H)+.

後処理

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. filtrationfiltered
  3. washthe resin washed with dichloromethane
  4. customThe solvent was removed in vacuo
  5. customthe crude material purified
  6. washeluting with 1-10% methanol (2 N ammonia)/dichloromethane

出典と根拠

ORDレコード
ord-05dd9e0b8908450e8b851a8eff8a7278
出典データセット
uspto-grants-2014_04
特許番号
US08691865B2

反応ノート

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