2-Butanone, 3-bromo- → 5-{1-[(4,5-Dimethyl-1,3-thiazol-2-yl)(methyl)sulfonimidoyl]ethyl}-2-(trifluoromethyl)pyridine

HRID 1895578Notes

Reaction equation

HRID 1895578 reaction equation
[CH3:1][S:2](=[O:19])([CH:7]([C:9]1[CH:10]=[N:11][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][CH:14]=1)[CH3:8])=[N:3][C:4]([NH2:6])=[S:5].Br[CH:21]([CH3:25])[C:22](=O)[CH3:23]>CCO>[CH3:25][C:21]1[N:6]=[C:4]([N:3]=[S:2]([CH:7]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:17])([F:18])[F:16])=[N:11][CH:10]=2)[CH3:8])([CH3:1])=[O:19])[S:5][C:22]=1[CH3:23]

Participants

4

Reactant 2

HCID 131422-Butanone, 3-bromo-HCID 44199436HCID 44199436, compound

Product 1

HCID 575544105-{1-[(4,5-Dimethyl-1,3-thiazol-2-yl)(methyl)sulfonimidoyl]ethyl}-2-(trifluoromethyl)pyridine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

In a microwave crimp tube, N-(methyl(oxo){1-[6-(trifluoromethyl)-3-pyridinyl]ethyl}-λ6-sulfanylidene)thiourea (J) (200 mg, 0.642 mmol) was suspended in EtOH (3 mL) and 3-bromobutan-2-one (151 mg, 69 μL, 0.642 mmol) was added via syringe, while stirring. The reaction was sealed and heated to 85° C. for 15 min in the microwave. The solvent was subsequently removed on the rotary evaporator and the remaining residue purified by preparative reverse phase chromatography (water/acetonitrile). 5-{1-[(4,5-dimethyl-1,3-thiazol-2-yl)(methyl)sulfonimidoyl]ethyl}-2-(trifluoromethyl)pyridine (67) was obtained in form of a slightly yellow oil as a 1:1 mixture of diastereomers (67 mg, 0.185 mmol, 29%). 1H-NMR (CDCl3, 400 MHz): δ=1.89 (d, J=7.2 Hz, 1.5H, CHCH3, diastereomer 1); 1.93 (d, J=7.2 Hz, 1.5H, CHCH3, diastereomer 2); 2.15 (s, 1.5H, thiazole-CH3, one diastereomer); 2.17 (s, 1.5H, thiazole-CH3, one diastereomer); 2.18 (s, 1.5H, thiazole-CH3, one diastereomer); 2.20 (s, 1.5H, thiazole-CH3, one diastereomer); 3.04 (s, 1.5H, S—CH3, diastereomer 1); 3.15 (s, 1.5H, S—CH3, diastereomer 2); 5.11 (q, J=7.2 Hz, 0.5H, CHCH3, diastereomer 1); 5.22 (q, J=7.2 Hz, 0.5H, CHCH3, diastereomer 2); 7.71 (d, J=8.1 Hz, 0.5H, pyr-C3-H, diastereomer 1), 7.73 (d, J=8.1 Hz, 0.5H, pyr-C3-H, diastereomer 2); 8.08 (dd, 3J=8.1 Hz, 4J=2.0 Hz, 0.5H, pyr-C4-H, diastereomer 1); 8.10 (dd, 3J=8.1 Hz, 4J=2.0 Hz, 0.5H, pyr-C4-H, diastereomer 2); 8.72 (d, 4J=2.0 Hz, 0.5H, pyr-C6-H, diastereomer 1); 8.78 (d, 4J=2.0 Hz, 0.5H, pyr-C6-H, diastereomer 2). 13C-NMR (CDCl3, 100 MHz): δ=10.9, 11.0 (thiazole-CH3, two diastereomers); 13.8, 14.4 (CHCH3, two diastereomers); 14.4 (double peak, thiazole-CH3, two diastereomers); 36.3, 36.5 (S—CH3, two diastereomers); 60.5, 61.2 (CHCH3, two diastereomers); 117.9, 118.0 (Ar, two diastereomers); 119.4, 119.5 (pyr-C, 2 diastereomers); 131.4, 132.1 (Ar, two diastereomers), 137.1, 137.4 (pyr-C, 2-diastereomers); 141.7, 141.9 (Ar, two diastereomers) 149.3, 149.4 (pyr-C, 2-diastereomers); 161.4, 161.7 (thiazole, two diastereomers); CF3, not detected. HPLC-MS (ESI+): mass calc'd for C14H17F3N3OS2 (M+H+): 364.1, found 364.5, HPLC-MS (ESI+) mass calc'd for C14H15F3N3OS2 (M−H+): 362.1, found 361.8.

Workup

  1. customThe reaction was sealed
  2. customThe solvent was subsequently removed on the rotary evaporator
  3. customthe remaining residue purified by preparative reverse phase chromatography (water/acetonitrile)

Sources & evidence

ORD record
ord-fabc5dd6eb2341a2a87df0f6bfb66046
Source dataset
uspto-grants-2013_08
Patent number
US08513462B2

Reaction notes

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