1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 66997255, compound

HRID 2363629Notes

Reaction equation

HRID 2363629 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[CH2:10][C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:17]([N:24]1[CH2:28][C@@H:27]2[C@@H:29]([NH2:32])[CH2:30][CH2:31][C@@H:26]2[CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.O.ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C>ClCCl>[CH2:17]([N:24]1[CH2:28][C@@H:27]2[C@@H:29]([NH:32][C:14]([C@@H:9]3[CH2:10][C@@H:11]([F:13])[CH2:12][N:8]3[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:16])[CH2:30][CH2:31][C@@H:26]2[CH2:25]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 12043048(2S,4R)-1-[(tert-butoxy)carbonyl]-4-fluoropyrrolidine-2-carboxylic acidHCID 66591011(3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine

Product 1

HCID 66997255HCID 66997255, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,4R)-1-(tert-butoxycarbonyl)-4-fluoropyrrolidine-2-carboxylic acid (2.87 g, 12.31 mmol) and (3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine from Example 33 Step A (2.93 g, 13.54 mmol) in dichloromethane (16.97 mL) was added 1-hydroxybenzotriazole hydrate (2.073 g, 13.54 mmol). After 2 minutes, N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (2.388 mL, 13.54 mmol) was added and the reaction was stirred at ambient temperature overnight. The reaction was quenched with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The solvent was removed in vacuo. The crude material was purified using an 80 g silica gel cartridge eluted with a gradient of 0-5% methanol (2 N ammonia)/dichloromethane over 20 minutes to give (2S,4R)-tert-butyl 2-((3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-ylcarbamoyl)-4-fluoropyrrolidine-1-carboxylate: 1H NMR (400 MHz, pyridine-d5) δ ppm 7.70 (s, 1H), 7.38-7.36 (m, 2H), 7.33-7.26 (m, 2H), 7.24-7.17 (m, 1H), 5.19 (dd, J=53.5, 3.3, 1H), 4.59 (t, J=7.8, 1H), 4.31-4.22 (m, 1H), 4.04-3.92 (m, 1H), 3.68 (dd, J=12.9, 3.7, 1H), 3.62-3.57 (m, 1H), 3.60-3.45 (m, 2H), 2.83-2.76 (m, 1H), 2.56-2.58 (m, 1H), 2.52-2.43 (m, 3H), 2.35 (m, 3H), 2.10 (dq, J=12.5, 6.3, 1H), 1.92-1.82 (m, 1H), 1.67-1.57 (m, 1H), 1.49 (s, 9H), 1.46-1.36 (m, 1H); MS (ESI+) m/z 432 (M+H)+.

Workup

  1. customThe reaction was quenched with saturated aqueous sodium bicarbonate solution
  2. extractionextracted with dichloromethane
  3. customThe solvent was removed in vacuo
  4. customThe crude material was purified
  5. washeluted with a gradient of 0-5% methanol (2 N ammonia)/dichloromethane over 20 minutes

Sources & evidence

ORD record
ord-21d3f26ad7ee4095bc81f967d785f6bd
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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