1-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl chloride → Tert-butyl 4-(2-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-5-methylpyrimidin-4-yl)benzoate

HRID 2401958Notes

Reaction equation

HRID 2401958 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.[NH2:18][C:19]1[N:24]=[C:23]([C:25]2[CH:37]=[CH:36][C:28]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:27][CH:26]=2)[C:22]([CH3:38])=[CH:21][N:20]=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:18][C:19]4[N:24]=[C:23]([C:25]5[CH:26]=[CH:27][C:28]([C:29]([O:31][C:32]([CH3:33])([CH3:34])[CH3:35])=[O:30])=[CH:36][CH:37]=5)[C:22]([CH3:38])=[CH:21][N:20]=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 57856165Tert-butyl 4-(2-amino-5-methylpyrimidin-4-yl)benzoate

Product 1

HCID 57856181Tert-butyl 4-(2-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-5-methylpyrimidin-4-yl)benzoate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

To 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarbonyl chloride (91 mg, 0.35 mmol) and tert-butyl 4-(2-amino-5-methylpyrimidin-4-yl)benzoate (50 mg, 0.175 mmol), pyridine (2 mL) was added. The reaction was heated at 90° C. for twenty four hours. The pyridine was evaporated under reduced pressure. The resulting mixture was dissolved in EtOAc 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 tert-butyl 4-(2-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-5-methylpyrimidin-4-yl)benzoate. ESI-MS m/z calc. 509.2, found 510.5 (M+1)+. Retention time 2.18 minutes.

Workup

  1. customThe pyridine was evaporated under reduced pressure
  2. dissolutionThe resulting mixture was dissolved in EtOAc
  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-763944f52bc34b17b49931cdb1a0d7fb
Source dataset
uspto-grants-2014_08
Patent number
US08796312B2

Reaction notes

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