1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Tert-butyl(s)-1-((3ar,4s,6as)-4-(2,2-bis(4-fluorophenyl)acetamido)hexahydrocyclopenta[c]pyrrol-2(1h)-yl)-4-methyl-1-oxopentan-2-yl(methyl)carbamate

HRID 2363611Notes

Reaction equation

HRID 2363611 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[C:9]([NH:11][C@@H:12]2[C@@H:19]3[C@@H:15]([CH2:16][NH:17][CH2:18]3)[CH2:14][CH2:13]2)=[O:10])=[CH:4][CH:3]=1.[C:27]([O:31][C:32]([N:34]([CH3:43])[C@@H:35]([CH2:39][CH:40]([CH3:42])[CH3:41])[C:36](O)=[O:37])=[O:33])([CH3:30])([CH3:29])[CH3:28].O.ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C>ClCCl>[F:26][C:23]1[CH:22]=[CH:21][C:20]([CH:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[C:9]([NH:11][C@@H:12]2[C@@H:19]3[C@@H:15]([CH2:16][N:17]([C:36](=[O:37])[C@@H:35]([N:34]([CH3:43])[C:32](=[O:33])[O:31][C:27]([CH3:29])([CH3:28])[CH3:30])[CH2:39][CH:40]([CH3:42])[CH3:41])[CH2:18]3)[CH2:14][CH2:13]2)=[O:10])=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7010555(2S)-2-{[(tert-butoxy)carbonyl](methyl)amino}-4-methylpentanoic acidHCID 665911952,2-bis(4-fluorophenyl)-N-[(3aR,4S,6aS)-octahydrocyclopenta[c]pyrrol-4-yl]acetamide

Product 1

HCID 66590861Tert-butyl(s)-1-((3ar,4s,6as)-4-(2,2-bis(4-fluorophenyl)acetamido)hexahydrocyclopenta[c]pyrrol-2(1h)-yl)-4-methyl-1-oxopentan-2-yl(methyl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2,2-Bis(4-fluorophenyl)-N-[(3aR,4S,6aS)-octahydrocyclopenta[c]pyrrol-4-yl]acetamide (30 mg, 0.084 mmol) and (S)-2-(tert-butoxycarbonyl(methyl)amino)-4-methylpentanoic acid (22.71 mg, 0.093 mmol) were dissolved in dichloromethane (0.5 mL) and then treated with 1-hydroxybenzotriazole hydrate (14.18 mg, 0.093 mmol). After 10 minutes, N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.016 mL, 0.093 mmol) was added, and the reaction mixture was stirred at ambient temperature overnight followed by quenching with water. The material in the organic layer was purified with a 4 g silica gel cartridge eluting with 1-10% methanol (2 N ammonia)/dichloromethane to give tert-butyl(S)-1-((3aR,4S,6aS)-4-(2,2-bis(4-fluorophenyl)acetamido)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-4-methyl-1-oxopentan-2-yl(methyl)carbamate: 1H NMR (400 MHz, pyridine-d5) δ ppm 8.25 (s, 1H), 7.46 (td, J=8.5, 5.5, 4H), 7.08-6.96 (m, 4H), 5.08 (s, 2H), 4.29-4.18 (m, 1H), 3.80 (s, 2H), 3.69 (s, 1H), 3.43 (dd, J=11.7, 3.5, 1H), 2.93 (s, 3H), 2.63 (s, 2H), 2.10 (td, J=12.9, 6.9, 1H), 1.91-1.69 (m, 3H), 1.63 (dt, J=13.2, 6.5, 2H), 1.51 (s, 9H), 1.40-1.26 (m, 1H), 0.97 (d, J=6.5, 3H), 0.92 (d, J=6.6, 3H); MS (ESI+) m/z 584 (M+H)+.

Workup

  1. customby quenching with water
  2. customThe material in the organic layer was purified with a 4 g silica gel cartridge
  3. washeluting with 1-10% methanol (2 N ammonia)/dichloromethane

Sources & evidence

ORD record
ord-1793804d133e484294ac834157946751
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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