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 2195064ノート

反応式

HRID 2195064 の反応式
[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]

参加物

8

反応物 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、化合物

生成物 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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6212Chloroform溶媒2 回HCID 31374Dimethylacetamide溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-abc22f6caa0a477e9260c24c107161bc
出典データセット
uspto-grants-2012_12
特許番号
US08334382B2

反応ノート

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