Pyridine → HCID 18327313, compound

HRID 1250176Notes

Reaction equation

HRID 1250176 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]=[N:11][N:10]([CH2:13][S:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]=1[NH2:21].N1C=CC=CC=1.[Cl:28][CH:29]([CH:33]1[CH2:36][CH2:35][CH2:34]1)[C:30](Cl)=[O:31]>CN(C)C=O>[Cl:28][CH:29]([CH:33]1[CH2:36][CH2:35][CH2:34]1)[C:30]([NH:21][C:9]1[N:10]([CH2:13][S:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:11]=[N:12][C:8]=1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])=[O:31]

Participants

5

Reactant 3

HCID 1049PyridineHCID 18327312HCID 18327312, compoundHCID 18327316HCID 18327316, compound

Product 1

HCID 18327313HCID 18327313, compoundYield 31,359.199%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.), stirred solution of 5-(2-fluorophenyl)-3-phenylsulfenylmethyl-3H-1,2,3-triazol-4-ylamine (1 g, 3.33 mmol) in dimethylformamide (15 ml) was added pyridine (460μl, 4.33 mmol) followed by 2-chloro-2-cyclobutylacetyl chloride (810 mg, 3.83 mmol) and the reaction stirred at 0° C. for 1 hour. The reaction was quenched by partitioning between ethyl acetate (100 ml) and water (100 ml). The layers were separated and the aqueous layer extracted with ethyl acetate (100 ml). The combined organic extracts were washed with citric acid (50 ml, 10% aqueous), sodium bicarbonate (50 ml, sat. aqueous), brine (50 ml). dried (Na2SO4) and the solvent removed in vacuo. The crude product was purified by flash chromatography (40% EtOAc/hexanes) to afford 2-chloro-2-cyclobutyl-N-[5-(2-fluorophenyl)-3-phenylsulfenylmethyl-3H-1,2,3-triazol-4-yl]acetamide (450 g, 31%; 52% based on recovered starting material) as a crystalline solid, m.p. 103-104° C.; δH (400 MHz, CDCl3) 1.79-2.18 (6H, m, CH(CH2)3), 2.83-2.93 (1H, m, CH(CH2)3), 4.28 (1H, d, J=8 Hz, CHCl), 5.58 (1H, d, J=14.3 Hz, PhSCH2A), 5.64 (1H, d, J=14.3 Hz, PhSCH2B), 7.10-7.16 (1H, m, ArH), 7.23-7.41 (7H, m, ArH), 7.79-7.85 (1H, m, ArH), 8.00-8.10 (1H, br m, NH); m/z (ES+) 431 (100%) (35ClM+H+), 433 (40%) (37 ClM+H+).

Workup

  1. customThe reaction was quenched
  2. customby partitioning between ethyl acetate (100 ml) and water (100 ml)
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with ethyl acetate (100 ml)
  5. washThe combined organic extracts were washed with citric acid (50 ml, 10% aqueous), sodium bicarbonate (50 ml, sat. aqueous), brine (50 ml)
  6. dry with materialdried (Na2SO4)
  7. customthe solvent removed in vacuo
  8. customThe crude product was purified by flash chromatography (40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-36f8feca878e43a5b7c0c73542f0a2ff
Source dataset
uspto-grants-2002_01
Patent number
US06337331B1

Reaction notes

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