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

HRID 1092555Notes

Reaction equation

HRID 1092555 reaction equation
[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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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 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)+.

Workup

  1. stirringThe reaction 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

Sources & evidence

ORD record
ord-42b3a8ece5f849829a14fed9a6f3524f
Source dataset
uspto-grants-2012_03
Patent number
US08129417B2

Reaction notes

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