Ethyl Acetate → tert-butyl (3-(5-methyl-2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate

HRID 527399ノート

反応式

HRID 527399 の反応式
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][CH2:12][O:13]C(C)=O.[C:17]([C:20]1[C:21]([NH:28][C:29]2[CH:30]=[C:31]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH:32]=[CH:33][CH:34]=2)=[N:22][C:23]([S:26][CH3:27])=[N:24][CH:25]=1)(=O)[CH3:18]>C1COCC1>[CH3:18][C:17]1[C:20]2[CH:25]=[N:24][C:23]([S:26][CH3:27])=[N:22][C:21]=2[N:28]([C:29]2[CH:30]=[C:31]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH:32]=[CH:33][CH:34]=2)[C:12](=[O:13])[CH:11]=1

参加物

5

反応物 3

HCID 8857Ethyl AcetateHCID 2733832Lithium HexamethyldisilazideHCID 86732010Tert-butyl (3-((5-acetyl-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate

生成物 1

HCID 86732009tert-butyl (3-(5-methyl-2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate収率 73.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

LiHMDS (1.0 M in THF, 27.3 mL, 27.3 mmol) was added to THF (100 mL) at −78° C. and treated with EtOAc (2.50 mL, 25.6 mmol) and stirred 15 min. tert-Butyl (3-((5-acetyl-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate (53) (3.19 g, 8.52 mmol) was added in one portion at −78° C. and the solution warmed to RT and stirred for 3 h. The reaction mixture was quenched with a saturated solution of NH4Cl and extracted with EtOAc (150 mL), washed with brine and dried over MgSO4, filtered and concentrated. Purification of the crude residue on silica gel column (10-90% EtOAc in hexanes) afforded the title compound (54) (2.49 g, 6.25 mmol, 73% yield) as a light yellow amorphous solid. m/z (ESI, +ve ion) 398.9 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 8.72 (1H, s), 7.46 (1H, br. s.), 7.42 (1H, t, J=8.0 Hz), 7.31 (1H, dd, J=8.2, 1.4 Hz), 6.87-6.94 (1H, m), 6.50-6.59 (2H, m), 2.50 (3H, d, J=1.0 Hz), 2.17 (3H, s), 1.50 (9H, s).

後処理

  1. additionwas added in one portion at −78° C.
  2. customThe reaction mixture was quenched with a saturated solution of NH4Cl
  3. extractionextracted with EtOAc (150 mL)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude residue on silica gel column (10-90% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-33306a6caa304968a9d7e0f866a6c5ba
出典データセット
uspto-grants-2016_05
特許番号
US09346801B2

反応ノート

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