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

HRID 613918Notes

Reaction equation

HRID 613918 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.[CH2:33]([O:40][C:41](=[O:66])[CH2:42][C@@H:43]([C:47]1[CH:51]=[CH:50][N:49]([C:52]2[CH:57]=[CH:56][C:55]([C:58]3[CH:63]=[CH:62][C:61]([C:64]#[N:65])=[CH:60][CH:59]=3)=[CH:54][CH:53]=2)[CH:48]=1)[C:44](O)=[O:45])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[NH2:67][C@H:68]([C:73]1[NH:74][CH:75]=[CH:76][N:77]=1)[CH2:69][CH:70]([CH3:72])[CH3:71].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[CH2:33]([O:40][C:41](=[O:66])[CH2:42][C@@H:43]([C:47]1[CH:51]=[CH:50][N:49]([C:52]2[CH:57]=[CH:56][C:55]([C:58]3[CH:59]=[CH:60][C:61]([C:64]#[N:65])=[CH:62][CH:63]=3)=[CH:54][CH:53]=2)[CH:48]=1)[C:44]([NH:67][C@H:68]([C:73]1[NH:77][CH:76]=[CH:75][N:74]=1)[CH2:69][CH:70]([CH3:72])[CH3:71])=[O:45])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=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 540329802(S)-[1-(4'-cyanobiphenyl-4-yl)-1H-pyrrol-3-yl]succinic acid 4-benzyl ester

Product 1

HCID 599327543(S)-[1-(4'-cyanobiphenyl-4-yl)-1H-pyrrol-3-yl]-N-[1(S)-(1H-imidazol-2-yl)-3-methylbutyl]succinamic acid benzyl esterYield 49%

Procedure

According to the procedure described in Example 1(b) for the preparation of 3(R)-t-butoxycarbonylamino-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid benzyl ester, 2(S)-[1-(4'-cyanobiphenyl-4-yl)-1H-pyrrol-3-yl]succinic acid 4-benzyl ester (prepared as described in Example 14(b)) and 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) were coupled with TBTU to provide a 49% yield of 3(S)-[1-(4'-cyanobiphenyl-4-yl)-1H-pyrrol-3-yl]-N-[1(S)-(1H-imidazol-2-yl)-3-methylbutyl]succinamic acid benzyl ester: mp 186-188° C. (dec); 1HNMR (DMSO-d6) δ 11.79 (s, 1H), 8.40 (d, 1H, J=8.5 Hz), 7.92 (s, 4H), 7.85 (d, 2H, J=8.5 Hz), 7.62 (d, 2H, J=8.8 Hz), 7.34 (s, 5H), 6.97 (s, 1H), 6.84 (s, 1H), 6.20 (s, 1H), 5.13-5.00 (m, 3H), 3.96 (dd, 1H, J=9.9, 5.5 Hz), 2.99 (dd, 1H, J=16.4, 10.8 Hz), 2.78 (dd, 1H, J=16.4, 5.0 Hz), 1.67-1.60 (m, 2H), 1.55-1.45 (m, 1H), 0.85 (d, 3H, J=6.6 Hz), 0.81 (d, 3H, J=6.3 Hz); Anal. Calculated for C36H35N5O3.H2O: C, 71.62; H, 6.18; N, 11.60. Found: C, 71.50,71.45; H, 5.97, 6.01; N, 11.51, 11.48.

Sources & evidence

ORD record
ord-722d09d370ee4a748eda3aba407a9fa6
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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