4-Methylmorpholine → {[2-{2-(S)-[(1-Amino-isoquinolin-6-ylmethyl)-carbamoyl]-pyrrolidin-1-yl}-1-(R)-(4-methoxybenzyl)-2-oxo-ethyl]-tert.-butoxycarbonyl-amino}-acetic acid ethyl ester

HRID 636992Notes

Reaction equation

HRID 636992 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[CH2:5][N:6]([C@H:14]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22](O)=[O:23])=[O:16])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH3:2].[NH2:35][CH2:36][C:37]1[CH:38]=[C:39]2[C:44](=[CH:45][CH:46]=1)[C:43]([NH2:47])=[N:42][CH:41]=[CH:40]2.CN1CCOCC1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:34])[CH2:5][N:6]([C@H:14]([CH2:25][C:26]1[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=1)[C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22](=[O:23])[NH:35][CH2:36][C:37]1[CH:38]=[C:39]2[C:44](=[CH:45][CH:46]=1)[C:43]([NH2:47])=[N:42][CH:41]=[CH:40]2)=[O:16])[C:7]([O:9][C:10]([CH3:12])([CH3:13])[CH3:11])=[O:8])[CH3:2]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 221697756-(Aminomethyl)isoquinolin-1-amineHCID 57033331{[2-{2(S)-Carboxy-pyrrolidin-1-yl}-1-(R)-(4-methoxybenzyl)-2-oxo-ethyl]-tert.-butoxycarbonyl-amino}-acetic acid ethyl ester

Product 1

HCID 57174480{[2-{2-(S)-[(1-Amino-isoquinolin-6-ylmethyl)-carbamoyl]-pyrrolidin-1-yl}-1-(R)-(4-methoxybenzyl)-2-oxo-ethyl]-tert.-butoxycarbonyl-amino}-acetic acid ethyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of {[2-{2-(S)-Carboxy-pyrrolidin-1-yl}-1-(R)-(4-methoxybenzyl)-2-oxo-ethyl]-tert.-butoxycarbonyl-amino}-acetic acid ethyl ester (0.240 g), 6-aminomethyl-isoquinolin-1-ylamine (0.092 g), N-methyl morpholine (0.170 mL) and 0.160 g of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) in 8 mL of dry N,N-dimethyl formamide was stirred for 3 h at ambient temperature. Removal of the solvent in vacuo followed by purification of the remaining residue by silica chromatography (dichloromethane/methanol 80/20) gave 0.310 g (100%) of the title compound as a light yellow solid. (+)-APCI-MS: 634 (MH+).

Workup

  1. customRemoval of the solvent in vacuo
  2. customfollowed by purification of the remaining residue by silica chromatography (dichloromethane/methanol 80/20)

Sources & evidence

ORD record
ord-a547bdeead3a4c1e9cfc17bbc48edfcc
Source dataset
uspto-grants-2001_02
Patent number
US06194409B1

Reaction notes

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