Diisopropylcarbodiimide → HCID 178451940, compound

HRID 2273045Notes

Reaction equation

HRID 2273045 reaction equation
[NH2:1][CH:2]1[CH2:5][CH:4]([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[N:13]=[C:14]([C@@H:17]4[CH2:21][CH2:20][CH2:19][N:18]4[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[NH:15][CH:16]=3)=[CH:8][CH:7]=2)[CH2:3]1.[N:29]1([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:36][CH2:35][CH2:34][C@H:30]1[C:31](O)=[O:32].CC(C)N=C=NC(C)C>ClCCl>[C:25]([O:24][C:22]([N:18]1[CH2:19][CH2:20][CH2:21][C@H:17]1[C:14]1[NH:15][CH:16]=[C:12]([C:9]2[CH:10]=[CH:11][C:6]([CH:4]3[CH2:3][CH:2]([NH:1][C:31]([C@@H:30]4[CH2:34][CH2:35][CH2:36][N:29]4[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:32])[CH2:5]3)=[CH:7][CH:8]=2)[N:13]=1)=[O:23])([CH3:28])([CH3:27])[CH3:26]

Participants

5

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 178451923HCID 178451923, compound

Product 1

HCID 178451940HCID 178451940, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-tert-butyl 2-(4-(4-(3-aminocyclobutyl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (A9) (330 mg, 0.86 mmol) in dichloromethane (60 mL), N-Boc-L-Pro-OH (204 mg, 0.95 mmol), and DIC (0.2 mL) were added at rt. After stirring overnight, the reaction mixture was diluted with methylene chloride (50 mL), and washed with saturated aqueous NaHCO3, dried with Na2SO4. After removal of the solvent, the crude product was purified by silica gel column chromatography (n-hexane/ethyl acetate=2:1) to afford the product (S)-tert-butyl 2-(3-(4-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)phenyl)cyclobutylcarbamoyl)pyrrolidine-1-carboxylate (A10) (294 mg, 59% yield).

Workup

  1. washwashed with saturated aqueous NaHCO3
  2. dry with materialdried with Na2SO4
  3. customAfter removal of the solvent
  4. customthe crude product was purified by silica gel column chromatography (n-hexane/ethyl acetate=2:1)

Sources & evidence

ORD record
ord-b4050ec9e0bb49b2a192641f434b254d
Source dataset
uspto-grants-2015_09
Patent number
US09120779B2

Reaction notes

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