Diisopropylethylamine → (S)-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-cyclohexyl-acetic acid methyl ester

HRID 1970618Notes

Reaction equation

HRID 1970618 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=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[CH3:51][O:52][C:53](=[O:62])[CH:54]([NH2:61])[CH:55]1[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]1>CN(C=O)C.C(Cl)CCl>[CH3:51][O:52][C:53](=[O:62])[C@@H:54]([NH:61][C:27]([C:18]1[CH:17]=[C:16]([O:15][CH2:14][C:13]([N:9]2[CH2:10][CH2:11][CH2:12][C@H:8]2[C:6](=[O:7])[NH:5][CH:1]2[CH2:4][CH2:3][CH2:2]2)=[O:30])[N:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:19]=1)=[O:28])[CH:55]1[CH2:56][CH2:57][CH2:58][CH2:59][CH2:60]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 22259438Methyl a-amino-cyclohexaneacetate HClHCID 668546955-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 66856691(S)-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-cyclohexyl-acetic acid methyl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 250 mg 5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid in 4 ml DMF were added 124 mg HOAt, 174 mg EDC, 0.37 ml DIPEA and 126 mg amino cyclohexylacetic acid methyl ester hydrochloride. After stirring for 12 h it was concentrated and the residue dissolved in dichloromethane. It was extracted with aqueous LiCl (4% w/w), aqueous NaHCO3 and 0.1 M HCl. The organic layer was dried over MgSO4 and concentrated to furnish the crude coupling product as colorless oil. Yield: 428 mg.

Workup

  1. concentrationwas concentrated
  2. dissolutionthe residue dissolved in dichloromethane
  3. extractionIt was extracted with aqueous LiCl (4% w/w), aqueous NaHCO3 and 0.1 M HCl
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customto furnish the crude coupling product as colorless oil

Sources & evidence

ORD record
ord-2a5739bf82c447baabb398e9dba3766d
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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