Cesium carbonate → 4-(4-(3-(2,4-dichlorophenoxy)azetidin-1-yl)pyrimidin-2-ylamino)-N-methylbenzamide

HRID 522907Notes

Reaction equation

HRID 522907 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:11][CH:10]([O:12][C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[CH2:9]2)[CH:5]=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:31]=[CH:30][C:25]([C:26]([NH:28][CH3:29])=[O:27])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O>[Cl:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[O:12][CH:10]1[CH2:11][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:21][C:22]3[CH:23]=[CH:24][C:25]([C:26]([NH:28][CH3:29])=[O:27])=[CH:30][CH:31]=3)[N:7]=2)[CH2:9]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 2355164-Amino-N-methylbenzamideHCID 866852552-Chloro-4-(3-(2,4-dichlorophenoxy)azetidin-1-yl)pyrimidine

Product 1

HCID 673551644-(4-(3-(2,4-dichlorophenoxy)azetidin-1-yl)pyrimidin-2-ylamino)-N-methylbenzamideYield 29%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of 2-chloro-4-(3-(2,4-dichlorophenoxy)azetidin-1-yl)pyrimidine (0.200 g, 609 mmoL) and 4-amino-N-methylbenzamide (0.109 g, 0.731 mmoL) in dimethyl acetamide (5 mL) was added cesium carbonate (300 mg, 9.14 mmol) and the reaction mixture was degassed for 15 min. Tris(dibenzylideneacetone)dipalladium (0) [Pd2(dba)3](0.030 g, 0.03 mmoL) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl [BINAP] (0.020 g, 0.03 mmoL) were added and the mixture was irradiated in the microwave at 120° C. for 1 h. Then the reaction was quenched with water and extracted with EtOAc (2×25 mL). The organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography provided 4-(4-(3-(2,4-dichlorophenoxy)azetidin-1-yl)pyrimidin-2-ylamino)-N-methylbenzamide (0.077 g, 29%) as solid. Observed mass (M+1): 443.9.

Workup

  1. customthe reaction mixture was degassed for 15 min
  2. additionTris(dibenzylideneacetone)dipalladium (0) [Pd2(dba)3](0.030 g, 0.03 mmoL) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl [BINAP] (0.020 g, 0.03 mmoL) were added
  3. customthe mixture was irradiated in the microwave at 120° C. for 1 h
  4. customThen the reaction was quenched with water
  5. extractionextracted with EtOAc (2×25 mL)
  6. washThe organic extracts were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customPurification by silica gel column chromatography

Sources & evidence

ORD record
ord-eede4a1393374044915130319e99f6f7
Source dataset
uspto-grants-2016_05
Patent number
US09334269B2

Reaction notes

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