Toluene → 2-(difluoro(3-fluorophenoxy)methyl)-3-(3-fluoro-4-morpholinophenyl)-6-methyl-pyrimidin-4(3H)-one

HRID 56296노트

반응식

HRID 56296 반응식
[F:1][C:2]1[CH:3]=[C:4]([NH:14][C:15](=[O:20])[CH2:16][C:17](=O)[CH3:18])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[F:21][C:22]([F:34])([O:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=1)[C:23]([NH2:25])=O.C1(C)C=CC=CC=1.[NH4+].[Cl-]>C1(C)C(C)=CC=CC=1.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.[Ti+4]>[F:34][C:22]([F:21])([O:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=1)[C:23]1[N:14]([C:4]2[CH:5]=[CH:6][C:7]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[C:2]([F:1])[CH:3]=2)[C:15](=[O:20])[CH:16]=[C:17]([CH3:18])[N:25]=1

참가 물질

7

반응물 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 900229102,2-Difluoro-2-(3-fluorophenoxy)acetamideHCID 90023295N-(3-fluoro-4-morpholinophenyl)-3-oxobutanamide

생성물 1

HCID 900230612-(difluoro(3-fluorophenoxy)methyl)-3-(3-fluoro-4-morpholinophenyl)-6-methyl-pyrimidin-4(3H)-one수율 40%

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매HCID 7237O-Xylene용매

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온도
165 °C

실험 절차

A mixture of N-(3-fluoro-4-morpholinophenyl)-3-oxobutanamide (0.60 g, 2.14 mmol), 2,2-difluoro-2-(3-fluorophenoxy)acetamide (0.88 g, 4.29 mmol) and titanium tetraisopropanolate (4.87 g, 17.1 mmol) in xylene (20 mL) was stirred at 165° C. for 24 h. The mixture was cooled to rt and 60 mL of toluene and 80 mL of saturated NH4Cl aqueous solution were added. The resulting mixture was stirred at rt overnight and filtered and the filtrate was extracted with DCM (150 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1) to give the title compound as a yellow solid (0.38 g, 40%). The compound was characterized by the following spectroscopic data:

후처리

  1. temperatureThe mixture was cooled to rt
  2. stirringThe resulting mixture was stirred at rt overnight
  3. filtrationfiltered
  4. extractionthe filtrate was extracted with DCM (150 mL×3)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1)

출처 및 근거

ORD 기록
ord-15ae61c5b24a4e61bf8b2381320619c2
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434695B2

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