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

HRID 1993749Notes

Reaction equation

HRID 1993749 reaction equation
[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

Participants

12

Reactant 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

Product 1

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

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

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 8, 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, 3.5μ, 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.

Workup

  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

Sources & evidence

ORD record
ord-f75ab2fc04b8492cb3246eea4993ac32
Source dataset
uspto-grants-2010_01
Patent number
US07652018B2

Reaction notes

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