Hydrochloric Acid → HCID 86693846, compound

HRID 516645Notes

Reaction equation

HRID 516645 reaction equation
[C:1]([C:3]1[CH:8]=[C:7]([C:9]2[C:10]([C:20]3[C:21]([F:41])=[C:22]([N:26](COC)[S:27]([C:30]4[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=4[F:37])(=[O:29])=[O:28])[CH:23]=[CH:24][CH:25]=3)=[N:11][N:12]([CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH:13]=2)[CH:6]=[CH:5][N:4]=1)#[N:2].Cl.[O:43]1CCOCC1>O.[OH-].[Na+]>[F:37][C:31]1[CH:32]=[CH:33][C:34]([F:36])=[CH:35][C:30]=1[S:27]([NH:26][C:22]1[C:21]([F:41])=[C:20]([C:10]2[C:9]([C:7]3[CH:6]=[CH:5][N:4]=[C:3]([C:1]([NH2:2])=[O:43])[CH:8]=3)=[CH:13][N:12]([CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=2)[CH:25]=[CH:24][CH:23]=1)(=[O:29])=[O:28]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66729498HCID 66729498, compound

Product 1

HCID 86693846HCID 86693846, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of N-{3-[4-(2-cyano-pyridin-4-yl)-1-(tetrahydro-pyran-4-yl)-1H-pyrazol-3-yl]-2-fluoro-phenyl}-2,5-difluoro-N-methoxymethyl-benzenesulfonamide (60 mg, 0.103 mmol) in dioxane (2 mL) concentrated HCl was added (0.5 mL) and the mixture was stirred at room temperature overnight. After two more additions of concentrated HCl (0.5 mL each) and 5 more hours of stirring, the reaction mixture was diluted with water and neutralized with 32% NaOH. It was then extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure, A 1.1 mixture of the title product and 4-[3-(3-{[(2,5-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]pyridine-2-carboxamide was obtained. The two products were separated by flash chromatography on silica gel (gradient cyclohexane/AcOEt 2:8 to pure AcOEt), giving 21 mg of the title compound and 15 mg of 4-[3-(3-{[(2,5-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]pyridine-2-carboxamide as white solids. HPLC (254 nm): Rt: 6.26 min; 1H NMR (DMSO-d6) Shift: 10.67 (s, 1H), 8.59 (s, 1H), 8.52 (d, J=5.2 Hz, 1H), 7.80 (s, 1H), 7.62-7.51 (m, 1H), 7.51-7.43 (m, 1H), 7.43-7.31 (m, 3H), 7.31-7.22 (m, 2H), 4.58-4.36 (m, 1H), 3.98 (dd, J=3.0, 11.7 Hz, 2H), 3.58-3.41 (m, 2H), 2.16-2.04 (m, 2H), 2.04-1.84 (m, 2H); HRMS (ESI) calcd for C26H21F3N5O3S [M+H]+ 540.1312. found 540.1332.

Workup

  1. extractionIt was then extracted with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. additionA 1.1 mixture of the title product

Sources & evidence

ORD record
ord-237adaa931f34fcda6eec67d8791a75f
Source dataset
uspto-grants-2015_08
Patent number
US09114137B2

Reaction notes

Loading…