1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[(3aS,4S,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-yl]-3-methyl-2-phenylbutanamide

HRID 1092472Notes

Reaction equation

HRID 1092472 reaction equation
[CH3:1][CH:2]([CH3:13])[CH:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=O.O.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.[CH2:36]([N:43]1[CH2:47][C@H:46]2[C@@H:48]([NH2:51])[CH2:49][CH2:50][C@H:45]2[CH2:44]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>ClCCl>[CH2:36]([N:43]1[CH2:47][C@H:46]2[C@@H:48]([NH:51][C:4](=[O:6])[CH:3]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:2]([CH3:1])[CH3:13])[CH2:49][CH2:50][C@H:45]2[CH2:44]1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 190243-Methyl-2-phenylbutanoic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 25918979(3AS,4S,6AR)-2-Benzyloctahydrocyclopenta[C]pyrrol-4-amine

Product 1

HCID 66590813N-[(3aS,4S,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-yl]-3-methyl-2-phenylbutanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3-Methyl-2-phenylbutanoic acid (1.049 mmol), 1-hydroxybenzotriazole hydrate (1.049 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (185 μL, 1.049 mmol) were combined in dichloromethane (4 mL). The mixture was stirred at room temperature for 10 minutes, then (3aS,4S,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine (1.049 mmol) from Step C was added in 2 mL of dichloromethane. The reaction was stirred at room temperature for 3.5 hours, and then quenched with 0.5 mL of water. The organic layer was separated and chromatographed using a silica gel cartridge (Analogix®, Burlington, Wis., RS-12) eluting with 1-10% methanol(ammonia)/dichloromethane to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.08 (dd, J=7.2, 14.4, 1H), 7.64 (dd, J=7.5, 14.5, 1H), 7.56-7.52 (m, 1H), 7.43 (d, J=4.4, 2H), 7.42-7.40 (m, 1H), 7.38-7.22 (m, 5H), 4.40 (dt, J=7.2, 14.3, 0.5H), 4.35-4.28 (m, 0.5H), 3.55 (d, J=12.7, 0.5H), 3.40 (dd, J=4.5, 12.8, 1H), 3.26 (d, J=12.9, 0.5H), 3.15 (d, J=10.5, 0.5H), 3.05 (d, J=10.5, 0.5H), 2.83-2.74 (m, 1H), 2.70-2.55 (m, 1.5H), 2.43-2.26 (m, 3H), 2.23-2.13 (m, 1H), 1.94-1.83 (m, 1H), 1.74-1.57 (m, 1.5H), 1.50 (dt, J=7.1, 15.3, 0.5H), 1.37 (td, J=6.5, 12.1, 0.5H), 1.31-1.23 (m, 0.5H), 1.18 (d, J=6.5, 1.5H), 1.10 (dt, J=6.5, 11.5, 0.5H), 1.03 (d, J=6.5, 1.5H), 0.73 (dd, J=6.7, 10.7, 3H); MS (ESI+) m/z 377 (M+H)+.

Workup

  1. stirringThe reaction was stirred at room temperature for 3.5 hours
  2. customquenched with 0.5 mL of water
  3. customThe organic layer was separated
  4. customchromatographed
  5. washeluting with 1-10% methanol(ammonia)/dichloromethane

Sources & evidence

ORD record
ord-05022c24ae5b4f22a0c9fafdc605bf69
Source dataset
uspto-grants-2012_03
Patent number
US08129417B2

Reaction notes

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