Lithium diisopropylamide → HCID 67261191、化合物

HRID 410571ノート

反応式

HRID 410571 の反応式
[Li+].CC([N-]C(C)C)C.[CH:9]1([C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[CH:25]=[C:24]([C:26]4[S:30][CH:29]=[N:28][CH:27]=4)[CH:23]=[C:22]([F:31])[CH:21]=3)[N:13]=2)[CH2:11][CH2:10]1.[C:32]([Si:36]([CH3:43])([CH3:42])[O:37][CH2:38][C:39]([CH3:41])=[O:40])([CH3:35])([CH3:34])[CH3:33]>O1CCCC1>[Si:36]([O:37][CH2:38][C:39]([C:29]1[S:30][C:26]([C:24]2[CH:23]=[C:22]([F:31])[CH:21]=[C:20]([NH:19][C:14]3[N:13]=[C:12]([CH:9]4[CH2:11][CH2:10]4)[C:17]([F:18])=[CH:16][N:15]=3)[CH:25]=2)=[CH:27][N:28]=1)([OH:40])[CH3:41])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:43])[CH3:42]

参加物

5

反応物 3

HCID 2724682Lithium diisopropylamideHCID 41249691-(tert-Butyldimethylsilyloxy)-2-propanoneHCID 67257916HCID 67257916、化合物

生成物 1

HCID 67261191HCID 67261191、化合物収率 64%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

実験手順

LDA (0.757 mL, 1.362 mmol) was added to tetrahydrofuran (4 mL) at −78° C. After 15 minutes at −78° C., a solution of the product of Step 4 (150 mg, 0.454 mmol) in tetrahydrofuran (4 mL) was added dropwise. After 30 minutes at −78° C., a solution of 1-{[tert-butyl(dimethyl)-silyl]oxy}acetone (0.110 mL, 0.568 mmol) in tetrahydrofuran (4 mL) was added dropwise at −78° C. The reaction mixture was allowed to warm to ambient temperature. After 1 hour, the reaction mixture was quenched with saturated ammonium chloride, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate and hexanes to afford 1-{[tert-butyl(dimethyl)silyl]oxy}-2-(5-{3-[(4-cyclopropyl-5-fluoropyrimidin-2-yl)amino]-5-fluorophenyl}-1,3-thiazol-2-yl)propan-2-ol (150 mg, 0.29 mmol, 64%). MS ESI: [M+H]+ m/z 519.2.

後処理

  1. waitAfter 30 minutes at −78° C.
  2. waitAfter 1 hour
  3. customthe reaction mixture was quenched with saturated ammonium chloride
  4. additiondiluted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel
  10. washeluting with ethyl acetate and hexanes

出典と根拠

ORDレコード
ord-3a02a0dfe6f94975b34612ae44ae066f
出典データセット
uspto-grants-2014_06
特許番号
US08759366B2

反応ノート

読み込み中…