Dimethyl Sulfoxide → 4-{5-Chloro-2-[(1,1-dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile

HRID 1436435Notes

Reaction equation

HRID 1436435 reaction equation
C(Cl)(=O)C([Cl:4])=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>[Cl:4][C:19]1[S:18][C:17]([NH:16][C:13]([CH3:15])([CH3:14])[CH:12]=[O:11])=[N:21][C:20]=1[C:22]1[CH:23]=[CH:24][C:25]([C:26]#[N:27])=[CH:28][CH:29]=1

Participants

7

Reactant 4

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

Product 1

HCID 866186144-{5-Chloro-2-[(1,1-dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrileYield 22%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A dry round bottom flask under nitrogen was charged with oxalyl chloride (2M solution in methylene chloride (9.15 mL, 18.3 mmol) and methylene chloride (125 mL) and cooled to −78° C. Dimethylsulfoxide was added dropwise (2.6 mL, 36.6 mmol) and the mixture was stirred for 10 min. A solution of 4-{2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}benzonitrile (2.5 g, 9.2 mmol), prepared in step 1 of Example 82, in 10 mL of tetrahydrofuran was added and the mixture stirred for 30 min. Triethylamine (7.9 mL, 55 mmol) was added and 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 (20% acetone in hexane) afforded 4-{5-chloro-2-[(1,1-dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile (0.60 g, 22%) as a yellow solid. HRMS: calcd for C14H12ClN3OS+H+, 306.04623; found (ESI, [M+H]+), 306.0453; Analytical HPLC: purity see MS. MS & UV are same at 210-370 nm; 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. additionwas added
  2. stirringthe mixture stirred for 30 min
  3. stirringthe mixture was stirred for 20 min
  4. temperatureto warm to 25° C
  5. washwashed with H2O, brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-ed9d7cda4d2a4313a45056ca0e45e352
Source dataset
uspto-grants-2009_11
Patent number
US07618990B2

Reaction notes

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