Dimethyl Sulfoxide → 4-{2-[(1,1-Dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile

HRID 1993747Notes

Reaction equation

HRID 1993747 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH2:12][C:13]([NH:16][C:17]1[S:18][CH:19]=[C:20]([C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=2)[N:21]=1)([CH3:15])[CH3:14].C(N(CC)CC)C>C(Cl)Cl.O1CCCC1>[CH3:15][C:13]([NH:16][C:17]1[S:18][CH:19]=[C:20]([C:22]2[CH:23]=[CH:24][C:25]([C:26]#[N:27])=[CH:28][CH:29]=2)[N:21]=1)([CH3:14])[CH:12]=[O:11]

Participants

7

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 866185984-{2-[(2-Hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}benzonitrile

Product 1

HCID 866186094-{2-[(1,1-Dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrileYield 61%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A 1M solution of oxalyl chloride in methylene chloride (20 mL, 20 mmol) was cooled to −78° C., dimethyl sulfoxide was added dropwise (1.77 mL, 25 mmol) and the mixture was stirred. This solution (5.5 mL, 5.5 mmol of activated dimethyl sulfoxide) was added via syringe to a solution of 4-{2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}benzonitrile (1.5 g, 5.5 mmol), prepared in step 1 of Example 7, in 60 mL of 5:1 methylene chloride:tetrahydrofuran that had been cooled to −78° C. The reaction was stirred for 30 min, triethylamine (1.6 mL, 11 mmol) was added, the mixture was stirred for 20 min, and then allowed to warm to 25° C. The mixture was then diluted with methylene chloride and washed with H2O, brine, dried over anhydrous MgSO4, filtered and concentrated. Flash chromatography (10%-20% acetone in hexane) afforded 4-{2-[(1,1-dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile (0.91 g, 61%) of as a white solid. HRMS: calcd for C14H13N3OS+H+, 272.08521; found (ESI, [M+H]+), 272.0853; Analytical HPLC: HPLC purity 100% at 210-370 nm, 9.1 min.; 100% at 328 nm, 9.1 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. stirringThe reaction was stirred for 30 min
  2. stirringthe mixture was stirred for 20 min
  3. washwashed with H2O, brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-1948af87ac9944b78112e301c8553b0a
Source dataset
uspto-grants-2010_01
Patent number
US07652018B2

Reaction notes

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