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 1524847Notes

Reaction equation

HRID 1524847 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-bdc40d1b1d6c45fc8ee7bc9d39459e50
Source dataset
uspto-grants-2015_07
Patent number
US09079916B2

Reaction notes

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