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

HRID 1993747노트

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HRID 1993747 반응식
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]

참가 물질

7

반응물 4

HCID 679Dimethyl Sulfoxide2회HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 866185984-{2-[(2-Hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}benzonitrile

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매3회HCID 8028Tetrahydrofuran용매

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온도
25 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-1948af87ac9944b78112e301c8553b0a
출처 데이터셋
uspto-grants-2010_01
특허 번호
US07652018B2

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