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

HRID 1503350
Notes
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Reaction equation

HRID 1503350 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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 730123151-(2-Chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carbaldehydeHCID 118024020HCID 118024020, compound

Product 1

HCID 86698985(3-methyl-1-(2-(1-methyl-1H-indol-5-ylamino)pyrimidin-4-yl)-1H-pyrazol-4-yl)methanol
Yield 72.2%

Reagents, catalysts & solvents 2

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

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

  1. customAfter being degassed by nitrogen bubbling
  2. additionTo the reaction mixture, water was added
  3. customto form solids
  4. filtrationThe resulting solids were collected by filtration
  5. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes