4-Methylmorpholine → (2-{2(S)-[(1-Amino-isoquinolin-6-ylmethyl)-carbamoyl]-pyrrolidin-1-yl}-2-oxo-1-(R)-phenyl-ethyl)-carbamic acid isopropyl ester

HRID 1008561Notes

Reaction equation

HRID 1008561 reaction equation
[CH:1]([O:4][C:5]([NH:7][C@H:8]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](O)=[O:17])=[O:10])=[O:6])([CH3:3])[CH3:2].[NH2:25][CH2:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[C:33]([NH2:37])=[N:32][CH:31]=[CH:30]2.CN1CCOCC1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C=O.CC(O)=O>[CH:1]([O:4][C:5](=[O:6])[NH:7][C@H:8]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:17])[NH:25][CH2:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[C:33]([NH2:37])=[N:32][CH:31]=[CH:30]2)=[O:10])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 221697756-(Aminomethyl)isoquinolin-1-amineHCID 229584901-[(R)-Isopropoxycarbonylamino-phenyl-acetyl]-pyrrolidine-2-(S)-carboxylic acid

Product 1

HCID 53885854(2-{2(S)-[(1-Amino-isoquinolin-6-ylmethyl)-carbamoyl]-pyrrolidin-1-yl}-2-oxo-1-(R)-phenyl-ethyl)-carbamic acid isopropyl esterYield 35%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-[(R)-isopropoxycarbonylamino-phenyl-acetyl]-pyrrolidine-2-(S)-carboxylic acid (0.20 g), 6-aminomethyl-isoquinolin-1-ylamine (0.6 mmol), N-methyl morpholine (0.2 mL) and 0.19 g of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) in 3 mL of dry N,N-dimethyl formamide was stirred for 3 h at ambient temperature. 0.120 mL CH3COOH were added, the mixture was concentrated and the remaining residue was purified by HPLC (RP-18; H2O/CH3OH 95/5→0/100) to give 0.10 g (35%) of the title compound as a colorless oil. (+)-APCI-MS: 490 (MH+).

Workup

  1. concentrationthe mixture was concentrated
  2. customthe remaining residue was purified by HPLC (RP-18; H2O/CH3OH 95/5→0/100)

Sources & evidence

ORD record
ord-efa99ec810ae4a2b9fffb0ebad9a202e
Source dataset
uspto-grants-2004_09
Patent number
US06797710B2

Reaction notes

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