Potassium Carbonate → N-(4-(1,2-dimethyl-1H-imidazol-5-yl)-2-methoxyphenyl)-7-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidin-2-amine

HRID 523052Notes

Reaction equation

HRID 523052 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[CH:11]=[CH:10][C:9]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)=[N:8][C:6]=2[N:7]=1.[CH3:18][N:19]1[C:23]([C:24]2[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([O:31][CH3:32])[CH:25]=2)=[CH:22][N:21]=[C:20]1[CH3:33].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:18][N:19]1[C:23]([C:24]2[CH:30]=[CH:29][C:27]([NH:28][C:2]3[N:3]=[CH:4][C:5]4[CH:11]=[CH:10][C:9]([C:12]5[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=5)=[N:8][C:6]=4[N:7]=3)=[C:26]([O:31][CH3:32])[CH:25]=2)=[CH:22][N:21]=[C:20]1[CH3:33]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 682913774-(1,2-Dimethyl-1H-imidazol-5-yl)-2-methoxyanilineHCID 899957352-chloro-7-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidine

Product 1

HCID 73389263N-(4-(1,2-dimethyl-1H-imidazol-5-yl)-2-methoxyphenyl)-7-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidin-2-amineYield 31.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

A suspension of 2-chloro-7-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidine (Preparation 55, 7.5 mg, 0.03 mmol), 4-(1,2-dimethyl-1H-imidazol-5-yl)-2-methoxyaniline (Preparation 74, 10 mg, 0.05 mmol), R-(+)BINAP (2 mg, 3 umol), Pd(OAc)2 (0.69 mg, 3 umol), K2CO3 (42 mg, 0.31 mmol) in DMF (3 mL) was stirred at 160° C. under microwave irradiation for 2 hours. The reaction mixture was filtered, diluted with NaCl solution and extracted with EtOAc. The organic layer was purified by SCX-2 column eluting with 2M NH3 in MeOH and concentrated in vacuo. The residue was purified by Biotage silica gel column chromatography eluting with 0-10% MeOH in EtOAc followed by preparative HPLC to afford the title compound (4 mg, 31%).

Workup

  1. filtrationThe reaction mixture was filtered
  2. additiondiluted with NaCl solution
  3. extractionextracted with EtOAc
  4. customThe organic layer was purified by SCX-2 column
  5. washeluting with 2M NH3 in MeOH
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by Biotage silica gel column chromatography
  8. washeluting with 0-10% MeOH in EtOAc

Sources & evidence

ORD record
ord-dff22bb4b9684790b62dc3b7881c24d9
Source dataset
uspto-grants-2016_05
Patent number
US09334286B2

Reaction notes

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