1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N2-(tert-butyloxycarbonyl)-N1-{(3aS,4R,6aR)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide

HRID 2363515Notes

Reaction equation

HRID 2363515 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].OC1C2N=NNC=2C=CC=1.[F:27][C:28]([F:46])([F:45])[C:29]1[CH:30]=[C:31]([CH:42]=[CH:43][CH:44]=1)[CH2:32][N:33]1[CH2:37][C@H:36]2[C@H:38]([NH2:41])[CH2:39][CH2:40][C@H:35]2[CH2:34]1.CN(C)CCCN=C=NCC>ClCCl>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([NH:41][C@H:38]1[C@H:36]2[C@H:35]([CH2:34][N:33]([CH2:32][C:31]3[CH:42]=[CH:43][CH:44]=[C:29]([C:28]([F:46])([F:27])[F:45])[CH:30]=3)[CH2:37]2)[CH2:40][CH2:39]1)=[O:16])[CH2:10][CH:11]([CH3:12])[CH3:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 66590435(3aS*,4R*,6aR*)-2-(3-(trifluoromethyl)benzyl)octahydrocyclopenta[c]pyrrol-4-amineHCID 178418300HCID 178418300, compound

Product 1

HCID 66590495N2-(tert-butyloxycarbonyl)-N1-{(3aS,4R,6aR)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(tert-Butoxycarbonyl)-L-leucine (180 mg, 0.778 mmol), hydroxybenzotriazole (119 mg, 0.778 mmol), and (3aS,4R,6aR)-2-(3-(trifluoromethyl)benzyl)octahydrocyclopenta[c]pyrrol-4-amine (201 mg, 0.707 mmol) from Example 154 Step A were combined in dichloromethane (1 mL). After 20 minutes, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (0.138 mL, 0.778 mmol) was added and the reaction stirred at room temperature for 24 hours. The reaction was quenched with water, and the layers were separated. The aqueous layer extracted with 1 mL of dichloromethane. The combined organic layers were applied to a silica gel cartridge (Analogix®, Burlington, Wis., RS15-24) and eluted with 1-10% methanol (2 N ammonia)/dichloromethane to give N2-(tert-butyloxycarbonyl)-N1-{(3aS,4R,6aR)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.66 (d, J=7.1, 1H), 7.97 (d, J=8.5, 1H), 7.73 (s, 1H), 7.56 (s, 2H), 7.44 (t, J=7.7, 1H), 4.70 (dd, J=5.9, 11.0, 1H), 4.40 (br s, 1H), 3.56 (d, J=13.5, 1H), 3.41 (d, J=13.5, 1H), 2.74 (d, J=8.9, 1H), 2.48 (s, 2H), 2.37-2.31 (m, 1H), 2.27 (d, J=8.4, 1H), 2.24-2.19 (m, 1H), 2.12 (dq, J=6.0, 12.0, 1H), 1.91-1.81 (m, 4H), 1.66 (td, J=7.4, 14.7, 1H), 1.50 (s, 9H), 1.43-1.35 (m, 1H), 0.87 (d, J=5.9, 3H), 0.84 (d, J=5.6, 3H); MS (ESI+) m/z 498 (M+H)+.

Workup

  1. customThe reaction was quenched with water
  2. customthe layers were separated
  3. extractionThe aqueous layer extracted with 1 mL of dichloromethane
  4. washeluted with 1-10% methanol (2 N ammonia)/dichloromethane

Sources & evidence

ORD record
ord-29dea640c16d41d6a0aad22f5a5b4ed0
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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