Acetic Acid → 4-[2-(3-Benzyl-5,5-dimethyl-2-oxoimidazolidin-1-yl)-1,3-thiazol-4-yl]benzonitrile

HRID 1436426ノート

反応式

HRID 1436426 の反応式
[CH3:1][C:2]([NH:6][C:7]1[S:8][CH:9]=[C:10]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=2)[N:11]=1)([CH3:5])[CH:3]=O.[C:20]([OH:23])(=O)C.[CH2:24]([NH2:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([BH3-])#N.[Na+].C(N(CC)CC)C.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.C([O-])(O)=O.[Na+]>CO.C(OCC)(=O)C.O1CCCC1.C(Cl)Cl>[CH2:24]([N:31]1[CH2:3][C:2]([CH3:5])([CH3:1])[N:6]([C:7]2[S:8][CH:9]=[C:10]([C:12]3[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=3)[N:11]=2)[C:20]1=[O:23])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

参加物

12

反応物 7

HCID 176Acetic AcidHCID 7504BenzylamineHCID 8471TriethylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 866186094-{2-[(1,1-Dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile

生成物 1

HCID 247832474-[2-(3-Benzyl-5,5-dimethyl-2-oxoimidazolidin-1-yl)-1,3-thiazol-4-yl]benzonitrile収率 60.1%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

4-{2-[(1,1-Dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile (290 mg, 1.07 mmol), prepared in step 1 of Example 83, was dissolved in methanol (8 mL) and tetrahydrofuran (2 mL) and then 1 g of molecular sieves was added. Acetic acid (0.12 mL, 2.1 mmol) and benzylamine (0.35 mL, 3.21 mmol) were added, followed by sodium cyanoborohydride (0.404 g, 6.42 mmol), and the mixture was stirred for 3 h. The mixture was diluted with ethyl acetate and washed with H2O, brine, dried over anhydrous MgSO4, filtered and concentrated to give 390 mg of crude product. This material was dissolved in 15 mL tetrahydrofuran and triethylamine (0.81 mL, 5.6 mmol) was added followed by triphosgene (0.48 g, 1.6 mmol). The mixture was stirred for 1 h, poured into saturated NaHCO3, diluted with methylene chloride and washed with H2O, 1N HCl, brine, dried over anhydrous MgSO4, filtered and concentrated. Flash chromatography (20% ethyl acetate/hexane) afforded the title compound (0.250 g, 60%) as a pale yellow solid. HRMS: calcd for C22H20N4OS+H+, 389.14306; found (ESI, [M+H]+), 389.1449; Analytical HPLC: 83.0% at 210-370 nm, 11.0 min; 84.4% at 252 nm, 11.0 min; the Xterra® RP18 column, 3.5%, 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. washwashed with H2O, brine
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give 390 mg of crude product
  6. stirringThe mixture was stirred for 1 h
  7. washwashed with H2O, 1N HCl, brine
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated

出典と根拠

ORDレコード
ord-0683f4b82e9842fb9437d4c0fe826f8d
出典データセット
uspto-grants-2009_11
特許番号
US07618990B2

反応ノート

読み込み中…