O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → N-[1(S)-(1H-imidazol-2-yl)-3-methylbutyl]-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester

HRID 382173Notes

Reaction equation

HRID 382173 reaction equation
C(OC(=O)C[C@@H](NC(OC(C)(C)C)=O)C(N[C@H](C(=O)NC)C(C)(C)C)=O)C1C=CC=CC=1.[NH2:33][C@H:34]([C:39]1[NH:40][CH:41]=[CH:42][N:43]=1)[CH2:35][CH:36]([CH3:38])[CH3:37].Cl.[CH2:45]([O:52][C:53](=[O:76])[CH2:54][C@@H:55]([N:59]1[CH:63]=[CH:62][C:61]([C:64]2[CH:69]=[CH:68][C:67]([C:70]3[CH:75]=[CH:74][N:73]=[CH:72][CH:71]=3)=[CH:66][CH:65]=2)=[CH:60]1)[C:56](O)=[O:57])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[CH2:45]([O:52][C:53](=[O:76])[CH2:54][C@@H:55]([N:59]1[CH:63]=[CH:62][C:61]([C:64]2[CH:65]=[CH:66][C:67]([C:70]3[CH:75]=[CH:74][N:73]=[CH:72][CH:71]=3)=[CH:68][CH:69]=2)=[CH:60]1)[C:56]([NH:33][C@H:34]([C:39]1[NH:43][CH:42]=[CH:41][N:40]=1)[CH2:35][CH:36]([CH3:38])[CH3:37])=[O:57])[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

5

Reactant 4

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 183412702-(1(S)-amino-3-methyl-butyl)-imidazoleHCID 537065323(R)-t-butoxycarbonylamino-N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)succinamic acid benzyl esterHCID 700979932(R)-[3-(4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinic acid 4-benzyl ester hydrochloride

Product 1

HCID 53669781N-[1(S)-(1H-imidazol-2-yl)-3-methylbutyl]-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl esterYield 41%

Procedure

According to the procedure described in Example 1(b) for the preparation of 3(R)-t-butyloxycarbonylamino-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid benzyl ester, 2-(1(S)-amino-3-methyl-butyl)-imidazole (See Chen, J. J.; Zhang, Y.; Hammond, S.; Dewdney, N.: Ho, T.; Browner, M. F.; Castelhano, A. L., submitted for publication; and Abel-Meguid, S. S.; Metcalf B. W.; Caw, T. J.; DeMarsh, P.; Des Jarlais, R. L.; Fisher, S.; Green, D. W.; et al. Biochemistry, 1994, 33, 11671-11677) and 2(R)-[3-(4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinic acid 4-benzyl ester hydrochloride (prepared as described in Example 7(a)) were coupled with TBTU. Flash column chromatography with 0-5% MeOH/CH2Cl2 gradient eluant and recrystallization from EtOAc gave in 41% yield N-[1(S)-(1H-imidazol-2-yl)-3-methylbutyl]-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester as white crystals, mp 179-81° C. (d).

Workup

  1. customFlash column chromatography with 0-5% MeOH/CH2Cl2 gradient eluant and recrystallization from EtOAc

Sources & evidence

ORD record
ord-95df6ad2e1694cdcafb8f0a695310553
Source dataset
uspto-grants-2001_10
Patent number
US06306892B1

Reaction notes

Loading…