Trifluoroacetic acid water → HCID 56653051, compound

HRID 516640Notes

Reaction equation

HRID 516640 reaction equation
C([NH:5][C:6]1[CH:11]=[C:10]([C:12]2[C:13]([C:19]3[C:20]([F:40])=[C:21]([N:25](COC)[S:26]([C:29]4[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=4[F:36])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=3)=[N:14][N:15]([CH2:17][CH3:18])[CH:16]=2)[CH:9]=[CH:8][N:7]=1)(C)(C)C.C(O)(C(F)(F)F)=O.O>>[NH2:5][C:6]1[CH:11]=[C:10]([C:12]2[C:13]([C:19]3[C:20]([F:40])=[C:21]([NH:25][S:26]([C:29]4[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=4[F:36])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=3)=[N:14][N:15]([CH2:17][CH3:18])[CH:16]=2)[CH:9]=[CH:8][N:7]=1

Participants

3

Reactant 2

HCID 22392675Trifluoroacetic acid waterHCID 66729372HCID 66729372, compound

Product 1

HCID 56653051HCID 56653051, compoundYield 37.8%

Procedure

N-{3-[4-(2-tert-Butylamino-pyridin-4-yl)-1-ethyl-1H-pyrazol-3-yl]-2-fluoro-phenyl}-2,5-difluoro-N-methoxymethyl-benzenesulfonamide (250 mg, 0.436 mmol) was treated with TFA/H2O 9:1 (3 mL) at 70° C. for 4.5 h. The reaction mixture was then evaporated to dryness, taken up with AcOEt and washed with sat, aq. NaHCO3 and brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (DCM/MeOH/NH3 7M in MeOH 90:8:2) and then treated with ethyl ether, filtered and dried to give 78 mg of N-{3-[4-(2-Amino-pyridin-4-yl)-1-ethyl-1H-pyrazol-3-yl]-2-fluoro-phenyl}-2,5-difluoro-benzene-sulfonamide as a white solid. HPLC (254 nm): Rt: 5.13 min; 1H NMR (DMSO-d6) Shift: 10.75 (br. s., 1H), 8.13 (s, 1H), 7.67 (dd, J=0.5, 5.4 Hz, 1H), 7.50-7.59 (m, 1H), 7.41-7.50 (m, 2H), 7.30 (td, J=24, 7.4 Hz, 1H), 7.12-7.26 (m, 2H), 6.27 (d, J=0.7 Hz, 1H), 6.08 (dd, J=14, 5.4 Hz, 1H), 5.82 (br. s., 2H), 4.18 (q, J=7.2 Hz, 2H), 1.42 (t, J=7.3 Hz, 3H); HRMS (ESI) calcd for C22H19F3N5O2S [M+H]+ 474.1206. found 474.1184.

Workup

  1. customThe reaction mixture was then evaporated to dryness
  2. washwashed
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by chromatography on silica gel (DCM/MeOH/NH3 7M in MeOH 90:8:2)
  6. additiontreated with ethyl ether
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-8f7dcc3c28d84fef9ce637e8ff55f089
Source dataset
uspto-grants-2015_08
Patent number
US09114137B2

Reaction notes

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