2-Dimethylaminopyridine → 3-(4-Tert-butoxy-phenyl)-2-{[7-cyclohexyl-6-(4-fluoro-phenyl)-pyrazolo[1,5-alpha]pyrimidine-3-carbonyl]-amino}-propionic acid tert-butyl ester

HRID 460705Notes

Reaction equation

HRID 460705 reaction equation
[CH:1]1([C:7]2[N:12]3[N:13]=[CH:14][C:15]([C:16](O)=[O:17])=[C:11]3[N:10]=[CH:9][C:8]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.CN(C1C=CC=CN=1)C.[NH2:44][C@H:45]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH2:46][C:47]1[CH:52]=[CH:51][C:50]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[CH:49][CH:48]=1.Cl.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.C(OCC)(=O)C>[C:61]([O:60][C:58](=[O:59])[CH:45]([NH:44][C:16]([C:15]1[CH:14]=[N:13][N:12]2[C:7]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[C:8]([C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)[CH:9]=[N:10][C:11]=12)=[O:17])[CH2:46][C:47]1[CH:48]=[CH:49][C:50]([O:53][C:54]([CH3:57])([CH3:55])[CH3:56])=[CH:51][CH:52]=1)([CH3:64])([CH3:63])[CH3:62]

Participants

8

Reactant 5

HCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 159581327-Cyclohexyl-6-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acidHCID 16219019(S)-tert-Butyl 2-amino-3-(4-(tert-butoxy)phenyl)propanoate hydrochloride

Product 1

HCID 697071743-(4-Tert-butoxy-phenyl)-2-{[7-cyclohexyl-6-(4-fluoro-phenyl)-pyrazolo[1,5-alpha]pyrimidine-3-carbonyl]-amino}-propionic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 15.0 mg (0.044 mmol) of 7-cyclohexyl-6-(4-fluoro-phenyl)-pyrazolo[1,5-α]pyrimidine-3-carboxylic acid in 2 mL of dimethylformamide (DMF) was added 0.019 mL (0.132 mmol) of diisopropylethylamine (DIEA), a few crystals of dimethylaminopyridine (DMAP cat), 17.4 mg (0.053 mmol) of H-Tyr(tBu)-OtBu.HCl, followed by 20 mg (0.053 mmol) of HATU, and the resulting mixture was stirred at rt overnight. The reaction mixture was diluted with ethyl acetate, washed with 0.1 N sodium hydroxide solution (2 times) and brine. The separated organic layer was dried over sodium sulfate and concentrated to give 3-(4-tert-butoxy-phenyl)-2-{[7-cyclohexyl-6-(4-fluoro-phenyl)-pyrazolo[1,5-α]pyrimidine-3-carbonyl]-amino}-propionic acid tert-butyl ester, which was used without any further purification in the next step.

Workup

  1. washwashed with 0.1 N sodium hydroxide solution (2 times) and brine
  2. dry with materialThe separated organic layer was dried over sodium sulfate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-4bdc752511de4d00a8d6bd3cda847ed0
Source dataset
uspto-grants-2007_03
Patent number
US07196111B2

Reaction notes

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