1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 66996989, compound

HRID 2363633Notes

Reaction equation

HRID 2363633 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:13][C@@H:12]2[C@@H:14]([NH2:17])[CH2:15][CH2:16][C@@H:11]2[CH2:10]1.[C:20]([O:24][C:25]([N:27]([CH3:36])[C@H:28]([C:33](O)=[O:34])[CH2:29][CH:30]([CH3:32])[CH3:31])=[O:26])([CH3:23])([CH3:22])[CH3:21].O.ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C>ClCCl>[CH3:36][N:27]([C@@H:28]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:33](=[O:34])[NH:17][C@@H:14]1[C@@H:12]2[C@@H:11]([CH2:10][N:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[C:2]([F:1])([F:18])[F:19])[CH2:13]2)[CH2:16][CH2:15]1)[C:25](=[O:26])[O:24][C:20]([CH3:23])([CH3:22])[CH3:21]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 701055553363-89-6HCID 66997589HCID 66997589, compound

Product 1

HCID 66996989HCID 66996989, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a 4 mL vial was added (3aR,4S,6aS)-2-(2-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrol-4-amine from Step 2 (21.6 mg, 0.080 mmol), N-(tert-butoxycarbonyl)-N-methyl-L-leucine (21.56 mg, 0.088 mmol), and 1-hydroxybenzotriazole hydrate (13.46 mg, 0.088 mmol) in dichloromethane (1 mL) to give a colorless solution. After 20 minutes, N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.016 mL, 0.088 mmol) was added. The reaction mixture was stirred at ambient temperature for 18 hours. The reaction was diluted with 1 mL of dichloromethane and quenched with 2 mL of water. The aqueous layer was extracted with more dichloromethane (2×2 mL), the solvent was removed in vacuo, and the crude material was applied to a 24 g silica gel cartridge and purified with 1-50% ethyl acetate/hexanes to give tert-butyl methyl((S)-4-methyl-1-oxo-1-((3aR,4S,6aS)-2-(2-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrol-4-ylamino)pentan-2-yl)carbamate: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.34 (d, J=6.8, 1H), 7.69-7.62 (m, 1H), 7.45 (t, J=7.4, 1H), 7.26 (d, J=8.2, 1H), 7.11 (t, J=7.6, 1H), 5.17 (s, 1H), 4.46 (s, 1H), 3.45 (d, J=8.8, 1H), 3.08 (d, J=24.1, 4H), 2.98-2.87 (m, 2H), 2.63 (s, 2H), 2.09 (s, 1H), 1.86 (ddd, J=23.7, 16.2, 10.4, 3H), 1.70-1.51 (m, 3H), 1.48 (s, 9H), 0.90 (d, J=6.5, 3H), 0.86 (d, J=6.5, 3H); MS (ESI+) m/z 498 (M+H)+.

Workup

  1. customto give a colorless solution
  2. customquenched with 2 mL of water
  3. extractionThe aqueous layer was extracted with more dichloromethane (2×2 mL)
  4. customthe solvent was removed in vacuo
  5. custompurified with 1-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1a1c9b9f050c4c6fa8960dbaf6310431
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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