Diethyl Ether → 4-Chloro-N-(6-methoxypyridin-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine

HRID 592471노트

반응식

HRID 592471 반응식
CCOCC.Cl[C:7]1[N:12]=[C:11]([Cl:13])[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=1.[NH2:18][C:19]1[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=1.CCN(CC)CC>CC(O)(C)C.ClCCCl.[Cl-].[Cl-].[Zn+2]>[Cl:13][C:11]1[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=[C:7]([NH:18][C:19]2[CH:24]=[N:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[N:12]=1

참가 물질

8

반응물 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 811216-Methoxy-3-pyridinylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidine

생성물 1

HCID 867123404-Chloro-N-(6-methoxypyridin-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 111,2-Dichloroethane용매2회HCID 6386tert-Butanol용매2회

실험 절차

A 1.0 M solution of ZnCl2 in Et2O (5.07 mL, 5.07 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (1.00 g, 4.61 mmol) in t-BuOH (25 mL) and DCE (25 mL). The mixture was stirred for 10 minutes and then diluted with t-BuOH (25 mL) and DCE (25 mL) before 5-amino-2-methoxypyridine (629 mg, 5.07 mmol) and Et3N (1.93 mL, 13.8 mmol) were added. The mixture was stirred at room temperature overnight and the volatiles were removed in vacuo. The resultant residue was suspended in water (250 mL) and sonicated for 10 minutes before the solid was isolated by vacuum filtration. The filter cake was washed with water and air dried and then dissolved in DCM and adsorbed onto silica gel. Purification by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) gave the title compound A68 as a white solid (944 mg, 67%). LCMS-A: rt 6.62 min; m/z 305 [M+H]+.

후처리

  1. additionwere added
  2. stirringThe mixture was stirred at room temperature overnight
  3. customthe volatiles were removed in vacuo
  4. customsonicated for 10 minutes before the solid
  5. customwas isolated by vacuum filtration
  6. washThe filter cake was washed with water and air
  7. customdried
  8. dissolutiondissolved in DCM
  9. customPurification by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

출처 및 근거

ORD 기록
ord-c6707c4b85e541d4856622a6374f7bcb
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238644B2

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