3,5-Dimethylpyrazole → 6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-3-(3,5-dimethyl-1H-pyrazol-1-yl)-7-fluoro-1,2-benzoxazole-5-carbaldehyde

HRID 577999Notes

Reaction equation

HRID 577999 reaction equation
Cl[C:2]1[C:6]2[CH:7]=[C:8]([CH:20]=[O:21])[C:9]([N:12]3[CH2:17][C@H:16]([CH3:18])[O:15][C@H:14]([CH3:19])[CH2:13]3)=[C:10]([F:11])[C:5]=2[O:4][N:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:30][C:31]1[CH:35]=[C:34]([CH3:36])[NH:33][N:32]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=CC=1.CCOC(C)=O.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH3:19][C@H:14]1[O:15][C@@H:16]([CH3:18])[CH2:17][N:12]([C:9]2[C:8]([CH:20]=[O:21])=[CH:7][C:6]3[C:2]([N:32]4[C:31]([CH3:30])=[CH:35][C:34]([CH3:36])=[N:33]4)=[N:3][O:4][C:5]=3[C:10]=2[F:11])[CH2:13]1

Participants

8

Reactant 4

HCID 62103,5-DimethylpyrazoleHCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 866581213-chloro-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzoxazole-5-carbaldehyde2×

Product 1

HCID 866581296-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-3-(3,5-dimethyl-1H-pyrazol-1-yl)-7-fluoro-1,2-benzoxazole-5-carbaldehyde

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred and degassed solution of 3-chloro-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzoxazole-5-carbaldehyde (Intermediate 534, 0.15 g, 0.48 mmol) in toluene was added K3PO4 (0.51 g, 2.40 mmol), 3,5-dimethyl-1H-pyrazole (92 mg, 0.96 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-phos) (4 mg, 0.009 mmol) and tris(dibenzylideneacetone) dipalladium(0) (8 mg, 0.009 mmol), sequentially and the reaction mixture was heated to 150° C. for 2 h in microwave reactor. The reaction mixture was diluted with EtOAc (15 mL). The organic layer was washed successively with water (2×10 mL), brine (2×10 mL), dried over anhydrous Na2SO4 and, after filtration, concentrated. The residue was purified over silica gel column using a gradient of ethylacetate in pet.ether to give product title compound as solid. Yield: 100 mg (56%).

Workup

  1. washThe organic layer was washed successively with water (2×10 mL), brine (2×10 mL)
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationafter filtration
  4. concentrationconcentrated
  5. customThe residue was purified over silica gel column

Sources & evidence

ORD record
ord-a19f735cdcbe4ad6acc46704b8721e89
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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