Trifluoroacetic anhydride → 6-{4-[6-(4-Fluoro-phenyl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-(R)-methyl-piperazin-1-yl}-5-methyl-pyridine-2-carboxylic acid methyl ester

HRID 1444129노트

반응식

HRID 1444129 반응식
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7](O)[N:6]=1)=[O:4].FC(F)(F)C(OC(=O)C(F)(F)F)=O.[F:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:38]=[C:37]([N:39]3[CH2:44][CH2:43][NH:42][CH2:41][C@H:40]3[CH3:45])[N:36]=[C:35]([N:46]3[CH2:50][CH2:49][CH2:48][C@H:47]3[CH3:51])[N:34]=2)=[CH:29][CH:28]=1.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl.CC(N(C)C)=O.O>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([N:42]2[CH2:43][CH2:44][N:39]([C:37]3[CH:38]=[C:33]([C:30]4[CH:29]=[CH:28][C:27]([F:26])=[CH:32][CH:31]=4)[N:34]=[C:35]([N:46]4[CH2:50][CH2:49][CH2:48][C@H:47]4[CH3:51])[N:36]=3)[C@H:40]([CH3:45])[CH2:41]2)[N:6]=1)=[O:4]

참가 물질

8

반응물 4

HCID 9845Trifluoroacetic anhydrideHCID 81531DiisopropylethylamineHCID 591683354-(4-Fluoro-phenyl)-6-(2-(R)-methyl-piperazin-1-yl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidineHCID 178497865HCID 178497865, 화합물

생성물 1

HCID 591683776-{4-[6-(4-Fluoro-phenyl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-(R)-methyl-piperazin-1-yl}-5-methyl-pyridine-2-carboxylic acid methyl ester

시약·촉매·용매 3

HCID 962Water용매HCID 6212Chloroform용매2회HCID 31374Dimethylacetamide용매

반응 조건

온도
100 °C

실험 절차

To a cold solution (0° C.) of 6-hydroxy-5-methyl-pyridine-2-carboxylic acid methyl ester (Adamczyk et. al. (2002) Tetrahedron 58:6951-6963) (167 mg, 1.0 mmol) in CHCl3 (15 mL), add trifluoroacetic anhydride (423 mg, 1.5 mmol) dropwise followed by TEA (202 mg, 2.0 mmol). Stir the mixture for 1 h. Dilute with CHCl3, wash with sat. NaHCO3, dry the organic layer (Na2SO4) and concentrate under reduced pressure. Mix the residue with 4-(4-fluoro-phenyl)-6-(2-(R)-methyl-piperazin-1-yl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine (426 mg, 1.2 mmol) and DIEA (129 mg, 1.0 mmol) in DMA. Heat the mixture at 100° C. for 16 h. Dilute with water, extract with EtOAc, and wash with brine. Dry the organic layer (Na2SO4) and concentrate under reduced pressure. Purify the residue by flash column eluting with EtOAc-Hexanes (1:5) to afford the title compound.

후처리

  1. washwash with sat. NaHCO3
  2. dry with materialdry the organic layer (Na2SO4)
  3. concentrationconcentrate under reduced pressure
  4. extractionextract with EtOAc
  5. washwash with brine
  6. dry with materialDry the organic layer (Na2SO4)
  7. concentrationconcentrate under reduced pressure
  8. customPurify the residue by flash column
  9. washeluting with EtOAc-Hexanes (1:5)

출처 및 근거

ORD 기록
ord-1918ba827d874eef9c007cb7136a18cc
출처 데이터셋
uspto-grants-2010_02
특허 번호
US07662830B2

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