Potassium Carbonate → (3-methyl-1-(2-(1-methyl-1H-indol-5-ylamino)pyrimidin-4-yl)-1H-pyrazol-4-yl)methanol

HRID 539895Notes

Reaction equation

HRID 539895 reaction equation
C[CH:2]([C:4]1[C:5]([CH3:16])=[N:6][N:7]([C:9]2[CH:14]=[CH:13][N:12]=[C:11](Cl)[N:10]=2)[CH:8]=1)[OH:3].[CH3:17][N:18]1[C:26]2[C:21](=[CH:22][C:23]([NH2:27])=[CH:24][CH:25]=2)[CH:20]=[CH:19]1.C(=O)([O-])[O-].[K+].[K+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:16][C:5]1[C:4]([CH2:2][OH:3])=[CH:8][N:7]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:27][C:23]3[CH:22]=[C:21]4[C:26](=[CH:25][CH:24]=3)[N:18]([CH3:17])[CH:19]=[CH:20]4)[N:10]=2)[N:6]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27695641-methyl-1H-indol-5-amineHCID 86698986methyl (1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazol-4-yl)methanol

Product 1

HCID 86698985(3-methyl-1-(2-(1-methyl-1H-indol-5-ylamino)pyrimidin-4-yl)-1H-pyrazol-4-yl)methanolYield 40.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A round bottomed flask was charged with methyl (1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazol-4-yl)methanol (400 mg, 1.78 mmol), 1-methyl-1H-indol-5-amine (338 mg, 1.3 equiv.), potassium carbonate (0.74 g, 3.0 equiv), palladium acetate (40 mg, 0.1 equiv), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (Xantphos, 206 mg, 0.2 equiv.) and 40 mL of anhydrous dioxane. After being degassed by nitrogen bubbling, the reaction mixture was heated at 100° C. for 12 hours. Volatiles were removed in vacuo and then the resulting residue was extracted with ethyl acetate. The collected organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting residue was purified by recrystallization in acetonitrile to give 241 mg (36%) of the desired product as a brown solid. MS (ESI) m/z 335 [M+H]+.

Workup

  1. customAfter being degassed by nitrogen bubbling
  2. customVolatiles were removed in vacuo
  3. extractionthe resulting residue was extracted with ethyl acetate
  4. dry with materialThe collected organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by recrystallization in acetonitrile

Sources & evidence

ORD record
ord-118ac1641f814d1089209b3e5e601e46
Source dataset
uspto-grants-2014_10
Patent number
US08871778B2

Reaction notes

Loading…