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

HRID 1503350Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([N:8]2[CH:12]=[C:11]([CH:13]=[O:14])[C:10]([CH3:15])=[N:9]2)[CH:5]=[CH:4][N:3]=1.[NH2:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([CH3:26])[CH:21]=[C:20]2C(C1CC1)=O.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>[CH3:15][C:10]1[C:11]([CH2:13][OH:14])=[CH:12][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:16][C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[N:22]([CH3:26])[CH:21]=[CH:20]4)[N:7]=2)[N:9]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A round bottomed flask was charged with 1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carbaldehyde (400 mg, 1.78 mmol), (5-amino-1-methyl-1H-indol-3-yl)(cyclopropyl)methanone (385 mg, 1.0 equiv.), potassium carbonate (0.74 g, 3.0 equiv), palladium acetate (20 mg, 0.05 equiv), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (Xantphos, 100 mg, 0.1 equiv.) and 40 mL of anhydrous dioxane. After being degassed by nitrogen bubbling, the reaction mixture was heated at 100° C. for 12 hours. To the reaction mixture, water was added to form solids. The resulting solids were collected by filtration, washed with water followed by ethyl acetate to give brown powder (430 mg, 60%). The collected solids were dried in vacuo and then used to next step without further purification; MS (ESI) m/z 401 [M+H]+.

Workup

customAfter being degassed by nitrogen bubbling
additionTo the reaction mixture, water was added
customto form solids
filtrationThe resulting solids were collected by filtration
washwashed with water

Sources & evidence

ORD record: ord-c09128f60ca54b208827822bf928df5a
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212178B2

Reaction notes

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