Toluene → HCID 58094879, compound

HRID 2282149Notes

Reaction equation

HRID 2282149 reaction equation
S(Cl)(Cl)=O.[C:5]([C:7]1[C:8]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=2[Cl:29])=[C:9]([C:19]([OH:21])=O)[S:10][C:11]=1[C:12]1[CH:17]=[CH:16][N:15]=[C:14]([F:18])[CH:13]=1)#[N:6].C1(C)C=CC=CC=1.C(Cl)Cl.Cl.[CH3:41][NH:42][O:43][CH3:44]>>[C:5]([C:7]1[C:8]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=2[Cl:29])=[C:9]([C:19]([N:42]([O:43][CH3:44])[CH3:41])=[O:21])[S:10][C:11]=1[C:12]1[CH:17]=[CH:16][N:15]=[C:14]([F:18])[CH:13]=1)#[N:6]

Participants

6

Reactant 5

HCID 1140TolueneHCID 6344Dichloromethane2×HCID 24386Thionyl ChlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 58095042HCID 58095042, compound

Product 1

HCID 58094879HCID 58094879, compoundYield 73.9%

Conditions

Temperature
90 °C

Procedure

Thionyl chloride (6.2 mL, 85 mmol) was added to a mixture of 4-cyano-3-(2,4-dichlorophenyl)-5-(2-fluoropyridin-4-yl)thiophene-2-carboxylic acid (2.94 g, 7.48 mmol) in Toluene (22 mL, 210 mmol) and the mixture was heated at 90° C. for 1 h. The reaction mixture was evaporated and the residue was coevaporated with toluene twice to thick oil. This oil in DCM (20 g, 200 mmol) was added to a mixture of N,O-Dimethylhydroxylamine Hydrochloride (2.92 g, 29.9 mmol) and TEA (7.0 mL, 5.0E1 mmol) in DCM (100 mL, 2000 mmol) in a ice bath. After 2 h, the mixture was washed by water and brine. The DCM layer was collected and dried and evaporated in vacuum to afford crude intermediate, which was purified by column chromatography to afford the title compound (2.41 g, 73.9%). LCMS: (FA) ES+, 436, 438. 1H NMR (400 MHz, d1-chloroform) δ: 8.41 (1H, d, J=5.26 Hz), 7.72-7.63 (1H, m), 7.54 (1H, d, J=1.96 Hz), 7.39 (2H, dd, J=7.70, 1.99 Hz), 7.29 (1H, d, J=8.26 Hz), 3.76 (3H, s), 3.27 (3H, s)

Workup

  1. customThe reaction mixture was evaporated
  2. washthe mixture was washed by water and brine
  3. customThe DCM layer was collected
  4. customdried
  5. customevaporated in vacuum
  6. customto afford crude intermediate, which
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-7c7cf18d2f394079b11e42fab21bccda
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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