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

HRID 1782163Notes

Reaction equation

HRID 1782163 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 88.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6212ChloroformSolvent2×

Procedure

To a solution of 5-amino-3-methylisothiazole-4-carbonitrile (method 4) (105.6 g, 0.76 mol) in pyridine (250 ml) at 0° C., isovaleryl chloride (100 g, 0.83 mol) in chloroform (300 ml) 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 (600 ml), washed with water (200 ml), 2N HCl (600 ml), satd. NaHCO3 (200 ml), brine (200 ml) and dried over Na2SO4Concentration 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 (149.7 g, 88%) 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 (600 ml)
  3. dry with materialNaHCO3 (200 ml), brine (200 ml) and dried over Na2SO4Concentration of the CHCl3 layer
  4. customprovided the crude product which
  5. customwas triturated from DCM/hexanes ( 1/10)
  6. filtrationfiltered off

Sources & evidence

ORD record
ord-c892cb4f85d94013a7c726f78c32171d
Source dataset
uspto-grants-2009_03
Patent number
US07498333B2

Reaction notes

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