Trifluoroacetic acid → HCID 18445857, compound

HRID 270960Notes

Reaction equation

HRID 270960 reaction equation
[CH:1]1([C:7]2[N:12]3[N:13]=[C:14]([CH3:19])[C:15]([C:16]([OH:18])=O)=[C:11]3[N:10]=[CH:9][C:8]=2[C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.C([O:40][C:41](=[O:56])[CH:42]([NH2:55])[CH2:43][C:44]1[CH:49]=[CH:48][C:47]([O:50]C(C)(C)C)=[CH:46][CH:45]=1)(C)(C)C.FC(F)(F)C(O)=O>CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C.O>[CH:1]1([C:7]2[N:12]3[N:13]=[C:14]([CH3:19])[C:15]([C:16]([NH:55][CH:42]([CH2:43][C:44]4[CH:45]=[CH:46][C:47]([OH:50])=[CH:48][CH:49]=4)[C:41]([OH:56])=[O:40])=[O:18])=[C:11]3[N:10]=[CH:9][C:8]=2[C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 81531DiisopropylethylamineHCID 4125399HCID 4125399, compoundHCID 15958181HCID 15958181, compound

Product 1

HCID 18445857HCID 18445857, compoundYield 16%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 36 mg (0.1 mmol) 7-cyclohexyl-6-(4-fluoro-phenyl)-2-methyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid in 2 mL of dimethylformamide was cooled at 0° C. To the above cold solution was added 0.053 mL (0.3 mmol) of N, N-diisopropylethylamine (DIEA), followed by 38 mg (0.1 mmol) of HA TU, and 37 mg (0.11 mmol) of 2-amino-3-(4-tert-butoxy-phenyl)-propionic acid tert-butyl ester, and a few crystals of 4-dimethylaminopyridine (DMAP), and the resulting mixture was allowed to warm up to rt, and stirred at rt overnight. The reaction mixture was then diluted with ethyl acetate, washed with 0.1 N NaOH solution, water, and brine, dried over sodium sulfate and evaporated to give a residue which was treated with 2 mL of 95:5 trifluoroacetic acid (TFA):water, and stirred at rt for 2.5 h. The mixture was quenched by the addition of 10 mL of 1:1 acetonitrile:water solution, and concentrated to give a residue which was purified via reverse-phase chromatography using Gilson to afford (after lyophilization) 8 mg (16% over 2 steps) of 2-{[7-Cyclohexyl-6-(4-fluoro-phenyl)-2-methyl-pyrazolo[1,5-a]pyrimidine-3-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid as a white solid (92% purity, entry 517), as indicated by 1H-NMR. (LC-MS calcd for C29H29FN4O4 [M+H]+ 517.22; found 517.2).

Workup

  1. washwashed with 0.1 N NaOH solution, water, and brine
  2. dry with materialdried over sodium sulfate
  3. customevaporated
  4. customto give a residue which
  5. customThe mixture was quenched by the addition of 10 mL of 1:1 acetonitrile
  6. concentrationwater solution, and concentrated
  7. customto give a residue which
  8. customwas purified via reverse-phase chromatography

Sources & evidence

ORD record
ord-37c6ec3ffa97414fac5fe58b1cfcde3e
Source dataset
uspto-grants-2008_11
Patent number
US07449488B2

Reaction notes

Loading…