1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Tert-butyl(s)-1-((3ar,4s,6as)-2-benzyloctahydrocyclopenta[c]pyrrol-4-ylamino)-4-methyl-1-oxopentan-2-ylcarbamate

HRID 2363546Notes

Reaction equation

HRID 2363546 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].O.ON1C2C=CC=CC=2N=N1.[CH2:28]([N:35]1[CH2:39][C@@H:38]2[C@@H:40]([NH2:43])[CH2:41][CH2:42][C@@H:37]2[CH2:36]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(N=C=NCCCN(C)C)C>ClCCl>[CH2:28]([N:35]1[CH2:39][C@@H:38]2[C@@H:40]([NH:43][C:14](=[O:16])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10][CH:11]([CH3:12])[CH3:13])[CH2:41][CH2:42][C@@H:37]2[CH2:36]1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 27960291-Hydroxybenzotriazole hydrateHCID 66591011(3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine

Product 1

HCID 90738969Tert-butyl(s)-1-((3ar,4s,6as)-2-benzyloctahydrocyclopenta[c]pyrrol-4-ylamino)-4-methyl-1-oxopentan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(tert-Butoxycarbonyl)-L-leucine (0.374 g, 1.617 mmol), 1-hydroxybenzotriazole hydrate (0.248 g, 1.617 mmol), and (3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine from Step A of Example 33 (0.318 g, 1.470 mmol) were combined in dichloromethane (3.0 mL). After 20 minutes, N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.286 mL, 1.617 mmol) was added, and the reaction was stirred at room temperature overnight. The reaction was quenched with water and extracted with dichloromethane (2×2 mL), and the extracts were applied directly to a 25 g silica gel cartridge and purified with a gradient of 5-40% acetone/hexanes over 30 minutes to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.61-8.64 (m, 1H), 7.96-7.99 (m, 1H), 7.42-7.44 (m, 2H), 7.36 (t, J=7.4 Hz, 2H), 7.28 (d, J=7.3 Hz, 1H), 4.65-4.73 (m, 1H), 4.37-4.45 (m, 1H), 3.59 (d, J=13.1 Hz, 1H), 3.43 (d, J=13.1 Hz, 1H), 2.81-2.84 (m, 1H), 2.55-2.58 (m, 1H), 2.44-2.54 (m, 2H), 2.24-2.36 (m, 2H), 2.02-2.13 (m, 1H), 1.78-1.94 (m, 4H), 1.53-1.66 (m, 1H), 1.50 (s, 9H), 1.26-1.43 (m, 1H), 0.87 (d, J=5.5 Hz, 3H), 0.83-0.85 (m, 3H); MS (ESI+) m/z 430 (M+H)+.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with dichloromethane (2×2 mL)
  3. custompurified with a gradient of 5-40% acetone/hexanes over 30 minutes

Sources & evidence

ORD record
ord-a6ab5d8ca5d249f3bf0c5a07e9ef2d4d
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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