Potassium Phosphate, Tribasic → HCID 178497013, compound

HRID 270977Notes

Reaction equation

HRID 270977 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:27]=[C:8]2[NH:9][C:10]([C:20]3[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=3)=[C:11]([CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)[C:12](=[O:13])[N:7]2[N:6]=1)=[O:4].[CH3:28][C:29]1(B(O)O)[CH:33]=[C:32]([CH3:34])[O:31][NH:30]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Pd].O1CCOCC1.ClCCl>[CH3:1][O:2][C:3]([C:5]1[CH:27]=[C:8]2[NH:9][C:10]([C:20]3[CH:25]=[CH:24][C:23]([C:33]4[C:29]([CH3:28])=[N:30][O:31][C:32]=4[CH3:34])=[CH:22][CH:21]=3)=[C:11]([CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)[C:12](=[O:13])[N:7]2[N:6]=1)=[O:4]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 668614323,5-Dimethyl-isoxazoleboronic acidHCID 178497012HCID 178497012, compound

Product 1

HCID 178497013HCID 178497013, compoundYield 37%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 42 mg (0.1 mmol) of 5-(4-bromo-phenyl)-6-cyclohexyl-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid methyl ester, 21 mg (0.15 mmol) of 3,5-dimethyl-isoxazoleboronic acid, 7.3 mg (0.01 mmol) of Pd catalyst, and 63 mg (0.3 mmol) of potassium phosphate in 1 mL of 1,4-dioxane was shaken at 95° C. in a sandbath overnight. The reaction mixture was then diluted with dichloromethane, filtered through a small pad of Celite, dried over sodium sulfate and evaporated to give a residue, which was purified via reverse-phase chromatography (Gilson) to afford desired 6-cyclohexyl-5-[4-(3,5-dimethyl-isoxazol-4-yl)-phenyl]-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid methyl ester as a solid as indicated by LC-MS—calcd for C25H26N4O4 [M++H]+: 447.19, found: 447.3. This material was then converted to 6-cyclohexyl-5-[4-(3,5-dimethyl-isoxazol-4-yl)-phenyl]-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid (591) via the well known LiOH saponification protocol (37% yield over 2 steps); LC-MS—calcd for C24H24N4O4 [M++H]+: 433.18, found: 433.1.

Workup

  1. filtrationfiltered through a small pad of Celite
  2. dry with materialdried over sodium sulfate
  3. customevaporated
  4. customto give a residue, which
  5. customwas purified via reverse-phase chromatography (Gilson)

Sources & evidence

ORD record
ord-d9087844bf114c4bb005846a1b3f8cce
Source dataset
uspto-grants-2008_11
Patent number
US07449488B2

Reaction notes

Loading…