1-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl chloride → 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(4-(6-methoxypyridin-3-yl)-5-methylpyrimidin-2-yl)cyclopropanecarboxamide

HRID 2401961Notes

Reaction equation

HRID 2401961 reaction equation
[F:1][C:2]1([F:17])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14](Cl)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[CH3:18][O:19][C:20]1[N:25]=[CH:24][C:23]([C:26]2[C:31]([CH3:32])=[CH:30][N:29]=[C:28]([NH2:33])[N:27]=2)=[CH:22][CH:21]=1>N1C=CC=CC=1>[F:1][C:2]1([F:17])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:33][C:28]4[N:27]=[C:26]([C:23]5[CH:24]=[N:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=5)[C:31]([CH3:32])=[CH:30][N:29]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1

Participants

4

Reactant 2

HCID 575168501-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl chlorideHCID 578561844-(6-Methoxypyridin-3-yl)-5-methylpyrimidin-2-amine

Product 1

HCID 578561031-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(4-(6-methoxypyridin-3-yl)-5-methylpyrimidin-2-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

To 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarbonyl chloride (369 mg, 1.42 mmol) and 4-(6-methoxypyridin-3-yl)-5-methylpyrimidin-2-amine (153 mg, 0.71 mmol), pyridine (4 mL) was added. The reaction was heated at 90° C. for three and a half hours. The pyridine was evaporated under reduced pressure. The resulting mixture was dissolved in ethyl acetate and filtered. The filtrate was washed with saturated aqueous NaHCO3 (×3). The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(4-(6-methoxypyridin-3-yl)-5-methylpyrimidin-2-yl)cyclopropanecarboxamide. ESI-MS m/z calc. 440.13, found 441.5 (M+1)+. Retention time 1.72 minutes.

Workup

  1. customThe pyridine was evaporated under reduced pressure
  2. dissolutionThe resulting mixture was dissolved in ethyl acetate
  3. filtrationfiltered
  4. washThe filtrate was washed with saturated aqueous NaHCO3 (×3)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. customevaporated under reduced pressure
  7. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-36b324102f924b70ba92c14f6c29220b
Source dataset
uspto-grants-2014_08
Patent number
US08796312B2

Reaction notes

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