p-Toluenesulfonic acid → HCID 66729606, compound

HRID 516637Notes

Reaction equation

HRID 516637 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[S:9]([N:12]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]2[N:23](C3CCCCO3)[N:24]=[CH:25][CH:26]=2)[C:17]=1[F:33])[CH2:13][O:14][CH3:15])(=[O:11])=[O:10].C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[S:9]([N:12]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]2[NH:23][N:24]=[CH:25][CH:26]=2)[C:17]=1[F:33])[CH2:13][O:14][CH3:15])(=[O:11])=[O:10]

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 66729575HCID 66729575, compound

Product 1

HCID 66729606HCID 66729606, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of crude 2,5-difluoro-N-{2-fluoro-3-[2-(tetrahydro-pyran-2-yl)-2H-pyrazol-3-yl]-phenyl}-N-methoxymethyl-benzene-sulfonamide (1.39 g) in MeOH (20 mL), p-toluenesulfonic acid (100 mg) was added and the solution was stirred at r.t. for 1 h. The reaction mixture was then concentrated under reduced pressure, taken up with AcOEt (100 mL) and washed with sat, aq. NaHCO3 (2×50 mL) and brine (50 mL). the organic phase was dried over Na2SO4 and evaporated to dryness. The crude product was purified by chromatography on silica gel (gradient cyclohexane/AcOEt 6:4 to 1:1) to give 630 mg of 2,5-difluoro-N-[2-fluoro-3-(2H-pyrazol-3-yl)-phenyl]-N-methoxymethyl-benzene-sulfonamide as a white powder (80% yield over two steps). HPLC (254 nm): Rt: 5.86 min; 1H NMR (DMSO-d6) Shift: 13.13 (br. s., 1H), 7.93-8.02 (m, 1H), 7.83 (br. s., 1H), 7.55-7.73 (m, 2H), 7.46-7.53 (m, 1H), 7.18-7.33 (m, 2H), 6.49 (br. s., 1H), 5.10 (s, 2H), 3.36-3.42 (m, 3H); HRMS (ESI) calcd for C17H15F3N3O3S [M+H]+ 3980781. found 398.0779.

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. washwashed
  3. dry with materialthe organic phase was dried over Na2SO4
  4. customevaporated to dryness
  5. customThe crude product was purified by chromatography on silica gel (gradient cyclohexane/AcOEt 6:4 to 1:1)

Sources & evidence

ORD record
ord-9e57f6baf2f64c6aae0f3bafc2c2bc47
Source dataset
uspto-grants-2015_08
Patent number
US09114137B2

Reaction notes

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