Dichloromethane → Methyl 4-(2,4-difluorophenyl)-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-1,3-thiazole-5-carboxylate

HRID 1530084Notes

Reaction equation

HRID 1530084 reaction equation
[CH3:1][C:2]1[C:24]([C:25]2[S:26][C:27](C3N=CN(C4CCCCO4)N=3)=[C:28](C3C=CC=CC=3)[N:29]=2)=[C:5]2[CH:6]=[C:7](OC3CCN(C(OC(C)(C)C)=O)CC3)[CH:8]=[CH:9][N:4]2[N:3]=1.[F:47][C:48]1[CH:53]=[C:52]([F:54])[CH:51]=[CH:50][C:49]=1B(O)O.[C:58](=[O:61])([O-])[O-:59].[Cs+].[Cs+].Cl[CH2:65]Cl.C(=O)(O)[O-].[Na+]>COCCOC.O.CCOC(C)=O>[F:47][C:48]1[CH:53]=[C:52]([F:54])[CH:51]=[CH:50][C:49]=1[C:28]1[N:29]=[C:25]([C:24]2[C:2]([CH3:1])=[N:3][N:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=23)[S:26][C:27]=1[C:58]([O:59][CH3:65])=[O:61]

Participants

9

Reactant 5

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 66854819tert-butyl 4-[(2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}pyrazolo[1,5-a]pyridin-5-yl)oxy]piperidine-1-carboxylate

Product 1

HCID 66854887Methyl 4-(2,4-difluorophenyl)-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-1,3-thiazole-5-carboxylateYield 864.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of methyl 2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-4-{[(trifluoromethyl)sulfonyl]oxy}-1,3-thiazole-5-carboxylate (100 mg, 0.237 mmol) obtained in Example 13-B (ii), 2,4-difluorophenylboronic acid (56.2 mg, 0.356 mmol), and cesium carbonate (154 mg, 0.474 mmol) in DME (5 mL) and water (1 mL) under argon atmosphere was added [1,1′-B is(diphenylphosphino)ferrocene]palladium(II) dichloride complex with dichloromethane (1:1) (19.4 mg, 0.0237 mmol) and the mixture was stirred for 80° C. To the mixture were added EtOAc (20 mL) and saturated aqueous solution of sodium bicarbonate (15 mL) and then organic layer was separated. The aqueous layer was extracted with EtOAc (5 mL) and the combined organic layer was washed with brine (5 mL). The organic layer was separated and then filtered through silica gel pad (3 g). After the concentration of the filtrate, the residue was washed with EtOAc (2 mL) to obtain title compound (79 mg, 87%) as a colorless solid.

Workup

  1. customorganic layer was separated
  2. extractionThe aqueous layer was extracted with EtOAc (5 mL)
  3. washthe combined organic layer was washed with brine (5 mL)
  4. customThe organic layer was separated
  5. filtrationfiltered through silica gel pad (3 g)
  6. washAfter the concentration of the filtrate, the residue was washed with EtOAc (2 mL)

Sources & evidence

ORD record
ord-998f66e555654077a5ceeb90131a3cbd
Source dataset
uspto-grants-2015_07
Patent number
US09090601B2

Reaction notes

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