1,4-Dioxane → HCID 178497014, compound

HRID 270978Notes

Reaction equation

HRID 270978 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].B1([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)C2CCCC1CCC2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>[Pd].C1COCC1.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]([CH2:37][C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)=[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

8

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 41509249-Benzyl-9-borabicyclo(3.3.1)nonaneHCID 178497012HCID 178497012, compound

Product 1

HCID 178497014HCID 178497014, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

According to a modification of a literature procedure (Suzuki, A. et al Tetrahedron Lett. 1986, 27, 6369-6372) a mixture of 43 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, 7.3 mg (0.01 mmol) of Pd catalyst, 0.4 mL (0.2 mmol) of B-Benzyl-9-BBN 0.5 M solution in THF, and 63 mg (0.3 mmol) of potassium phosphate, was purged with argon, 1 mL of 1,4-dioxane was added, and the resulting mixture was shaken at 80° 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 5-(4-benzyl-phenyl)-6-cyclohexyl-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 C27H27N3O3 [M++H]+: 442.21, found: 442.2. This material was then converted to 5-(4-benzyl-phenyl)-6-cyclohexyl-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid (581) via a LiOH saponification (33% yield over 2 steps); LC-MS—calcd for C26H25N3O3 [M++H]+: 428.19, found: 428.2.

Workup

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

Sources & evidence

ORD record
ord-3001d64e039b46c9bac0a71564329e8c
Source dataset
uspto-grants-2008_11
Patent number
US07449488B2

Reaction notes

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