Sodium hydride → Methyl (2E)-4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpent-2-enoate

HRID 1436430ノート

反応式

HRID 1436430 の反応式
[H-].[Na+].[CH3:3][O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].[CH3:14][C:15]([NH:19][C:20]1[S:21][CH:22]=[C:23]([C:25]2[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=2)[N:24]=1)([CH3:18])[CH:16]=O>O1CCCC1>[C:29]([C:28]1[CH:27]=[CH:26][C:25]([C:23]2[N:24]=[C:20]([NH:19][C:15]([CH3:18])([CH3:16])/[CH:14]=[CH:7]/[C:5]([O:4][CH3:3])=[O:6])[S:21][CH:22]=2)=[CH:32][CH:31]=1)#[N:30]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 866186094-{2-[(1,1-Dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile

生成物 1

HCID 86618612Methyl (2E)-4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpent-2-enoate収率 93%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a suspension of sodium hydride (60% in oil, 0.17 g, 4.5 mmol) in tetrahydrofuran (30 mL) was added trimethyl phosphonoacetate (0.75 mL, 5.2 mmol) dropwise and the mixture was stirred for 45 min. A solution of 4-{2-[(1,1-dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile (0.81 g, 3.0 mmol), prepared in step 1 of Example 83, in 5 mL of tetrahydrofuran was added and the mixture was stirred at 25° C. for 2 h. The reaction was quenched with saturated NH4Cl and diluted with ethyl acetate and washed with H2O, brine, dried over anhydrous MgSO4, filtered and concentrated. Flash chromatography (20% acetone/hexane) afforded methyl (2E)-4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpent-2-enoate (0.91 g, 93%) as a white solid. HRMS: calcd for C17H17N3O2S+H+, 328.11142; found (ESI, [M+H]+), 328.1135; Analytical HPLC: purity 100% at 210-370 nm, 9.9 min; 100% at 252 nm, 9.9 min; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min.

後処理

  1. additionwas added
  2. stirringthe mixture was stirred at 25° C. for 2 h
  3. customThe reaction was quenched with saturated NH4Cl
  4. additiondiluted with ethyl acetate
  5. washwashed with H2O, brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-93e9fec51a464378b144764fd9ee8bf8
出典データセット
uspto-grants-2009_11
特許番号
US07618990B2

反応ノート

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