Potassium Phosphate, Tribasic → N-[4-({3-Cyclopropyl-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}oxy)-3,5-difluorophenyl]acetamide

HRID 2192176Notes

Reaction equation

HRID 2192176 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[O:11][C:12]2[C:17]([F:18])=[CH:16][C:15]([NH:19][C:20](=[O:22])[CH3:21])=[CH:14][C:13]=2[F:23])[N:4]([S:24]([C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=2)(=[O:26])=[O:25])[CH:3]=1.[CH:34]1(B(O)O)[CH2:36][CH2:35]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[CH:34]1([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[CH:8][C:9]=3[O:11][C:12]3[C:17]([F:18])=[CH:16][C:15]([NH:19][C:20](=[O:22])[CH3:21])=[CH:14][C:13]=3[F:23])[N:4]([S:24]([C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[CH:3]=2)[CH2:36][CH2:35]1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 59741006N-[4-({3-Bromo-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}oxy)-3,5-difluorophenyl]acetamide

Product 1

HCID 59741001N-[4-({3-Cyclopropyl-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}oxy)-3,5-difluorophenyl]acetamide

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

1.00 g (1.86 mmol) of N-[4-({3-bromo-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}oxy)-3,5-difluorophenyl]acetamide, 1.12 g (13.1 mmol) of cyclopropylboronic acid (Wallace, Debra J.; Chen, Cheng-yi; Tetrahedron Lett. 2002, 43(39), 6987-6990), 52.3 mg (0.19 mmol) of tricyclohexylphosphine and 1.39 g (6.53 mmol) of potassium phosphate are suspended in 10 ml of toluene and 0.5 ml of water. The solution is degassed, and 20.9 mg (0.09 mmol) of palladium(II) acetate are added. The mixture is heated at 100° C. for 1.5 h. After cooling, ethyl acetate is added and the organic phase is separated off and washed twice with water. The organic phase is dried over sodium sulfate and concentrated. The product is purified by preparative HPLC.

Workup

  1. customThe solution is degassed
  2. temperatureAfter cooling
  3. customthe organic phase is separated off
  4. washwashed twice with water
  5. dry with materialThe organic phase is dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe product is purified by preparative HPLC

Sources & evidence

ORD record
ord-ef6747ea42574d43a07b33333ddc1c84
Source dataset
uspto-grants-2012_12
Patent number
US08329716B2

Reaction notes

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