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

HRID 613890Notes

Reaction equation

HRID 613890 reaction equation
[CH2:1]([O:8][C:9](=[O:32])[CH2:10][C@@H:11]([NH:24][C:25](OC(C)(C)C)=O)[C:12]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][CH3:22])[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[C:34](F)(F)[C:35](O)=O.[CH3:40][NH:41][C:42](=O)[C@H:43]([C:45]([CH3:48])(C)[CH3:46])N.CN(C(ON1N=N[C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][C:59]1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[CH2:1]([O:8][C:9](=[O:32])[CH2:10][C@@H:11]([N:24]1[CH:59]=[CH:64][C:63]([C:62]2[CH:61]=[CH:60][C:46]([C:45]3[CH:48]=[CH:40][N:41]=[CH:42][CH:43]=3)=[CH:35][CH:34]=2)=[CH:25]1)[C:12]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][CH3:22])[C:16]([CH3:19])([CH3:17])[CH3:18])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 18341348l-t-Leucine-n-methylamide trifluoroacetate saltHCID 537065323(R)-t-butoxycarbonylamino-N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)succinamic acid benzyl ester

Product 1

HCID 53931309N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(R)-[3-(4-(pyridin-4-yl)phenyl)-1H-pyrrol-1-yl]succinamic acid benzyl esterYield 86%

Procedure

According to the procedure described in Example 1(b) for the preparation of N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(R)-t-butoxycarbonylamino-succinamic acid benzyl ester, 2(R)-[3-(4'-pyridin-4-yl-phenyl)-1H-pyrrole-1-yl]succinic acid 4-benzyl ester hydrochloride and L-t-leucine-N-methylamide trifluoroacetate salt (prepared as described in Example 5(d)) were coupled with TBTU to provide in 86% yield N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(R)-[3-(4-(pyridin-4-yl)phenyl)-1H-pyrrol-1-yl]succinamic acid benzyl ester. 1H NMR: δ 8.80-8.57 (bs, 2H), 7.76-7.50 (m, 6H), 7.36-7.22 (m, 5H), 7.12 (d, 1H, J=1.6 Hz), 6.82 (t, 1H, J=1.9 Hz), 6.60 (dd, 1H, J=1.2, 1.2 Hz), 5.20-5.15 (m, 3H), 4.09 (dd, 1H, J=2.8,9.0 Hz), 3.41 (dd, 1H, J=5.3, 16.5 Hz), 3.10(dd, 1H, J=8.4, 16.5 Hz), 2.76 (dd, 3H, J=2.5, 4.4 Hz), 0.90 (s, 9H). IR (KBr): 3314, 2959, 1736, 1652, 1598, 1560, 1550, 1409, 1166 cm-1. LSIMS: 553 (MH+). Anal. Calculated for C33H36N4O4.0.5 H2O: C, 70.56; H, 6.64; N, 9.98. Found: C, 70.70; H, 6.62; N, 9.78.

Sources & evidence

ORD record
ord-5ae35885a71e40d482e915c3528c8713
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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