O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → N4-t-butyldiphenylsiloxy-N1-[2,2-Dimethyl-1(S)-(hydroxymethyl)propyl]-2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamide

HRID 566792Notes

Reaction equation

HRID 566792 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.[CH3:33][C:34]([CH3:64])([CH3:63])[C@H:35]([NH:38][C:39](=[O:62])[C@H:40]([N:45]1[CH:49]=[CH:48][C:47]([C:50]2[CH:55]=[CH:54][C:53]([C:56]3[CH:61]=[CH:60][N:59]=[CH:58][CH:57]=3)=[CH:52][CH:51]=2)=[CH:46]1)[CH2:41][C:42](O)=[O:43])[CH2:36][OH:37].[O:65]([NH2:83])[Si:66]([C:79]([CH3:82])([CH3:81])[CH3:80])([C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1)[C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CO.C(Cl)Cl>[O:65]([NH:83][C:42](=[O:43])[CH2:41][C@@H:40]([N:45]1[CH:49]=[CH:48][C:47]([C:50]2[CH:51]=[CH:52][C:53]([C:56]3[CH:57]=[CH:58][N:59]=[CH:60][CH:61]=3)=[CH:54][CH:55]=2)=[CH:46]1)[C:39]([NH:38][C@H:35]([CH2:36][OH:37])[C:34]([CH3:33])([CH3:64])[CH3:63])=[O:62])[Si:66]([C:79]([CH3:81])([CH3:80])[CH3:82])([C:73]1[CH:74]=[CH:75][CH:76]=[CH:77][CH:78]=1)[C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1

Participants

6

Reactant 4

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11737343O-(tert-Butyldiphenylsilyl)hydroxylamineHCID 15487948N-(2,2-dimethyl-1(S)-hydroxymethyl-propyl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acidHCID 537065323(R)-t-butoxycarbonylamino-N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)succinamic acid benzyl ester

Product 1

HCID 59932758N4-t-butyldiphenylsiloxy-N1-[2,2-Dimethyl-1(S)-(hydroxymethyl)propyl]-2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamideYield 43%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

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, N-(2,2-dimethyl-1(S)-hydroxymethyl-propyl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid (prepared as described in Example 5(a)) and t-butyldiphenylsiloxyamine were coupled with TBTU. Flash column chromatography with 0-5% MeOH/CH2Cl2 gradient eluant fumished in 43% yield N4-t-butyldiphenylsiloxy-N1-[2,2-Dimethyl-1(S)-(hydroxymethyl)propyl]-2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamide as an amorphous solid. 1H NMR (DMSO-d6): δ 10.73 (s, 1H), 8.59 (d, 2H, J=6.3 Hz), 7.85-7.70 (m, 5H), 7.65-7.56 (m, 6H), 7.45-7.34 (m, 6H), 7.29 (s, 1H), 6.79 (s, 1H), 6.43 (s, 1H), 5.20-5.14 (m, 1H), 4.38-4.36 (m, 1H), 3.54-3.50 (m, 2H), 2.82-2.70 (m, 1H), 0.99 (s, 9H), 0.84 (s, 9H). Anal: Calculated for C41H48N4O4Si•0.4 H2O: C, 70.74; H, 7.07; N, 8.05. Found: C, 70.83; H, 7.04; N, 8.33.

Sources & evidence

ORD record
ord-a1d17c33993147c79f004e1938be077c
Source dataset
uspto-grants-2001_01
Patent number
US06174915B1

Reaction notes

Loading…