1-Hydroxybenzotriazole → 4-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-5-(tert-butyl-diphenyl-silanyloxy)-pentanoyl]-piperazine-1-carboxylic acid butyl ester

HRID 1970582Notes

Reaction equation

HRID 1970582 reaction equation
[CH:1]1([NH:5][C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13](=[O:30])[CH2:14][O:15][C:16]2[N:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:19]=[C:18]([C:27](O)=[O:28])[CH:17]=2)=[O:7])[CH2:4][CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[CH2:51]([O:55][C:56]([N:58]1[CH2:63][CH2:62][N:61]([C:64](=[O:88])[C@@H:65]([NH2:87])[CH2:66][CH2:67][CH2:68][O:69][Si:70]([C:83]([CH3:86])([CH3:85])[CH3:84])([C:77]2[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=2)[C:71]2[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=2)[CH2:60][CH2:59]1)=[O:57])[CH2:52][CH2:53][CH3:54]>CN(C=O)C.C(Cl)CCl>[CH2:51]([O:55][C:56]([N:58]1[CH2:59][CH2:60][N:61]([C:64](=[O:88])[C@@H:65]([NH:87][C:27]([C:18]2[CH:17]=[C:16]([O:15][CH2:14][C:13]([N:9]3[CH2:10][CH2:11][CH2:12][C@H:8]3[C:6](=[O:7])[NH:5][CH:1]3[CH2:4][CH2:3][CH2:2]3)=[O:30])[N:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:19]=2)=[O:28])[CH2:66][CH2:67][CH2:68][O:69][Si:70]([C:83]([CH3:86])([CH3:85])[CH3:84])([C:77]2[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=2)[C:71]2[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=2)[CH2:62][CH2:63]1)=[O:57])[CH2:52][CH2:53][CH3:54]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 668546955-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acidHCID 668559754-[(S)-2-Amino-5-(tert-butyl-diphenyl-silanyloxy)-pentanoyl]-piperazine-1-carboxylic acid butyl ester hydrochloride

Product 1

HCID 866504734-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-5-(tert-butyl-diphenyl-silanyloxy)-pentanoyl]-piperazine-1-carboxylic acid butyl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 195 mg 5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid in 10 ml DMF were added 108 mg HOBt, 135 mg EDC and 0.2 ml DIPEA. After 20 minutes 255 mg 4-[(S)-2-Amino-5-(tert-butyl-diphenyl-silanyloxy)-pentanoyl]-piperazine-1-carboxylic acid butyl ester hydrochloride were added and the mixture stirred for 12 h. The reaction mixture was concentrated, diluted with ethyl acetate and washed with aqueous LiCl (4%), 0.1 M HCl and saturated aqueous NaHCO3. The crude product thus obtained was pure enough for the following transformation. Yield: 400 mg.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with ethyl acetate
  3. washwashed with aqueous LiCl (4%), 0.1 M HCl and saturated aqueous NaHCO3

Sources & evidence

ORD record
ord-e7e84a0a2f7c4117a889a9afb4e10512
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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