Methanol → HCID 22058242, compound

HRID 1828852Notes

Reaction equation

HRID 1828852 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:23](=[CH:24][CH:25]=1)[C:7]1[NH:8][N:9]=[C:10]([C:11]3[C:12]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[N:13][O:14][C:15]=3[CH3:16])[C:6]=1[CH2:5]2.C(N(CC)CC)C.[C]=O.[OH-:35].[Na+].[CH3:37][OH:38]>CN(C)C=O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:16][C:15]1[O:14][N:13]=[C:12]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:11]=1[C:10]1[NH:9][N:8]=[C:7]2[C:23]3[C:4]([CH2:5][C:6]=12)=[CH:3][C:2]([C:37]([OH:38])=[O:35])=[CH:25][CH:24]=3

Participants

9

Reactant 5

HCID 887MethanolHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 178418416HCID 178418416, compoundHCID 178434983HCID 178434983, compound

Product 1

HCID 22058242HCID 22058242, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-bromo-3-(5-methyl-3-phenylisoxazol-4-yl)-1,4-dihydroindeno[1,2-c]pyrazole (1 g, 2.6 mmol), triethylamine (0.7 ml, 5.2 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (178 mg, 0.32 mmol) in methanol (5 ml) and N,N-dimethylformamide (10 ml) in a sealed tube filled with carbon monoxide was added Pd(OAc)2 (36 mg, 0.16 mmol) and the mixture heated to 100° C. for 16 h. The solvent was evaporated, the residue dissolved in ethanol and treated with sodium hydroxide (13 mmol) at 0° C. and allowed to warm to RT. The solvent was evaporated, the residue partitioned between H2O and EtOAc and the product extracted into the aqueous layer which was then washed with diethyl ether (×3). The aqueous was cooled, acidified and extracted into EtOAc, the organic layer was then extracted with ammonium hydroxide solution (×2) and the aqueous cooled to 0° C. and acidified with conc HCl, left to stand at 0° C until the title compound appeared as a precipitate. 1H NMR (360 MHz, CDCl3) δ 8.08 (t, J=7.8 Hz, 1H), 7.77 (d, J=7.8 Hz, 1H), 7.51 (d, J=7.6 Hz, 1H), 7.45–7.35 (m, 3H), 7.30–7.13 (m, 4H), 3.16 (s, 2H), 2.59 (s, 3H), m/z (ES+) 358 (M+H)+.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue dissolved in ethanol
  3. temperatureto warm to RT
  4. customThe solvent was evaporated
  5. customthe residue partitioned between H2O and EtOAc
  6. extractionthe product extracted into the aqueous layer which
  7. washwas then washed with diethyl ether (×3)
  8. temperatureThe aqueous was cooled
  9. extractionextracted into EtOAc
  10. extractionthe organic layer was then extracted with ammonium hydroxide solution (×2)
  11. temperaturethe aqueous cooled to 0° C.
  12. waitleft
  13. customto stand at 0° C until the title compound

Sources & evidence

ORD record
ord-1d527ee997524036ac7e6ce2bec0f05e
Source dataset
uspto-grants-2006_06
Patent number
US07060710B2

Reaction notes

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