Hydrochloric Acid → HCID 86694536, compound

HRID 1406566Notes

Reaction equation

HRID 1406566 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[F:15][C:16]([C:19]1[CH:23]=[C:22]([NH2:24])[N:21]([C:25]2[CH:34]=[CH:33][CH:32]=[C:31]3[C:26]=2[CH:27]=[CH:28][CH:29]=[N:30]3)[N:20]=1)([F:18])[CH3:17].[OH-].[Li+].[OH-].[Na+].Cl>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:24][C:22]2[N:21]([C:25]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:26]=3[CH:27]=[CH:28][CH:29]=[N:30]4)[N:20]=[C:19]([C:16]([F:18])([F:15])[CH3:17])[CH:23]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 14798Sodium HydroxideHCID 1398824-t-Butylbenzenesulfonyl chlorideHCID 86694537HCID 86694537, compound

Product 1

HCID 86694536HCID 86694536, compoundYield 53.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 4-t-butylbenzene-1-sulfonyl chloride (0.080 g, 0.34 mmol), 3-(1,1-difluoroethyl)-1-(quinolin-5-yl)-1H-pyrazol-5-amine (0.045 g, 0.16 mmol), and DMAP (0.020 g, 0.16 mmol) in pyridine (1 mL) was heated at 85° C. for 5 h with stirring. After cooling to room temperature, 1 M aqueous lithium hydroxide (1 mL) and 1 M aqueous sodium hydroxide (1 mL) were added to the reaction mixture. The resulting mixture was heated at 75° C. for 1.5 h. After cooling to room temperature, the reaction mixture was neutralized with 1 N aqueous hydrochloric acid. The aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with aqueous saturated sodium bicarbonate, dried (Na2SO4), filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the title compound as a white solid (0.040 g, 0.085 mmol, 53%). 1H NMR (400 MHz, CD3OD) δ 10.70 (s, 1H), 8.88 (dd, J=1.6, 4.4 Hz, 1H), 8.14 (dd, J=1.2, 8.4 Hz, 1H), 7.77 (dd, J=7.2, 8.8 Hz, 1H), 7.64-7.61 (m, 2H), 7.52-7.42 (m, 5H), 7.31 (dd, J=1.2, 7.2 Hz, 1H), 1.96 (t, J=15.4 Hz, 3H), 1.35 (s, 9H); MS: (ES) m/z calculated for C24H25F2N4O2S [M+H]+ 471.2. found 471.2.

Workup

  1. temperatureAfter cooling to room temperature
  2. temperatureThe resulting mixture was heated at 75° C. for 1.5 h
  3. temperatureAfter cooling to room temperature
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×10 mL)
  5. washThe combined organic layers were washed with aqueous saturated sodium bicarbonate
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-19677bb440ae442d80041f9d27253c94
Source dataset
uspto-grants-2014_12
Patent number
US08916601B2

Reaction notes

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