Isovaleryl chloride → N-(4-Cyano-3-methyl-1,2-thiazol-5-yl)-3-methylbutanamide

HRID 1782140Notes

Reaction equation

HRID 1782140 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([CH3:7])[C:3]=1[C:8]#[N:9].[C:10](Cl)(=[O:15])[CH2:11][CH:12]([CH3:14])[CH3:13]>N1C=CC=CC=1.C(Cl)(Cl)Cl>[C:8]([C:3]1[C:4]([CH3:7])=[N:5][S:6][C:2]=1[NH:1][C:10](=[O:15])[CH2:11][CH:12]([CH3:14])[CH3:13])#[N:9]

Participants

5

Reactant 2

HCID 66054Isovaleryl chlorideHCID 14977025-amino-3-methylisothiazole-4-carbonitrile

Product 1

HCID 54757314N-(4-Cyano-3-methyl-1,2-thiazol-5-yl)-3-methylbutanamideYield 79%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6212ChloroformSolvent

Procedure

To a solution of 5-amino-3-methylisothiazole-4-carbonitrile (method 4) (6.38 g, 45.9 mmol) in pyridine (20 mL) at 0° C., isovaleryl chloride (6.65 g, 55 mmol) was added dropwise. After the completion of the addition the reaction mixture was allowed to warm to r.t. and stirred overnight. The TLC and the MS showed the complete disappearance of the starting material and the reaction mixture was diluted with CHCl3 (200 mL), washed with water (200 mL), 2N HCl (225 mL), satd. NaHCO3 (200 mL), brine (200 mL) and dried over Na2SO4. Concentration of the CHCl3 layer provided the crude product which was triturated from DCM/hexanes ( 1/10) and filtered off to isolate N-(4-cyano-3-methyl-isothiazol-5-yl)-3-methyl-butyramide (8.1 g, 79%) as an off-white crystalline solid. 1H NMR (300 MHz) δ 1.04 (d, 6H), 2.18-2.32 (m, 1H), 2.46 (d, 2H), 2.53 (s, 3H), 9.87 (bs, 1H).

Workup

  1. additionAfter the completion of the addition the reaction mixture
  2. washwashed with water (200 mL), 2N HCl (225 mL)
  3. dry with materialNaHCO3 (200 mL), brine (200 mL) and dried over Na2SO4
  4. customConcentration of the CHCl3 layer provided the crude product which
  5. customwas triturated from DCM/hexanes ( 1/10)
  6. filtrationfiltered off

Sources & evidence

ORD record
ord-0a6784ca2b954ddfa9449e001f3e6e0b
Source dataset
uspto-grants-2009_03
Patent number
US07498333B2

Reaction notes

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