Trifluoroacetic acid → 2-{[7-Cyclohexyl-6-(4-fluoro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid

HRID 270952Notes

Reaction equation

HRID 270952 reaction equation
C([O:5][C:6](=[O:45])[CH:7]([NH:20][C:21]([C:23]1[CH:24]=[N:25][N:26]2[C:31]([CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)=[C:30]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[CH:29]=[N:28][C:27]=12)=[O:22])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15]C(C)(C)C)=[CH:11][CH:10]=1)(C)(C)C.FC(F)(F)C(O)=O>O>[CH:32]1([C:31]2[N:26]3[N:25]=[CH:24][C:23]([C:21]([NH:20][CH:7]([CH2:8][C:9]4[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=4)[C:6]([OH:45])=[O:5])=[O:22])=[C:27]3[N:28]=[CH:29][C:30]=2[C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=2)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×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

Product 1

HCID 184458582-{[7-Cyclohexyl-6-(4-fluoro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acidYield 45%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A sample of crude 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 was treated with 1 mL of 95:5 trifluoroacetic acid (TFA):H2O and the resulting solution was stirred at rt for 1 h. Then the reaction mixture was quenched with 2 mL of 1:1 acetonitrile:water, concentrated, and the residue was purified via reverse-phase chromatography to afford (after lyophilization) 10 mg (45% yield over two steps) of desired 2-{[7-cyclohexyl-6-(4-fluoro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid (505) as a solid as indicated by 1H NMR; LC-MS calcd. for C28H27FN4O4 [M++H]+: 503.2; found: 503.2.

Workup

  1. customThen the reaction mixture was quenched with 2 mL of 1:1 acetonitrile
  2. concentrationwater, concentrated
  3. customthe residue was purified via reverse-phase chromatography

Sources & evidence

ORD record
ord-b16661b479bf4bbd90c7929f1537722b
Source dataset
uspto-grants-2008_11
Patent number
US07449488B2

Reaction notes

Loading…