Hydrochloric Acid → 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-[(methylsulfonyl)amino]-2H-indazole-3-carboxamide

HRID 63531Notes

Reaction equation

HRID 63531 reaction equation
[NH2:1][C:2]1[C:3]([CH:22]2[CH2:24][CH2:23]2)=[CH:4][C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)[C:6]=2[C:18]([NH:20][CH3:21])=[O:19].CCN(C(C)C)C(C)C.[CH3:34][S:35](Cl)(=[O:37])=[O:36].Cl.[OH-].[K+]>C(Cl)Cl.CCO.O>[Cl:17][C:14]1[CH:13]=[CH:12][C:11]([N:7]2[C:6]([C:18]([NH:20][CH3:21])=[O:19])=[C:5]3[C:9]([CH:10]=[C:2]([NH:1][S:35]([CH3:34])(=[O:37])=[O:36])[C:3]([CH:22]4[CH2:24][CH2:23]4)=[CH:4]3)=[N:8]2)=[CH:16][CH:15]=1

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 14797Potassium HydroxideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 67776316HCID 67776316, compound

Product 1

HCID 569631692-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-[(methylsulfonyl)amino]-2H-indazole-3-carboxamide

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (viii) (3.0 g, 8.8 mmol) in DCM (90 ml) was added DIPEA (5.4 mL, 30.8 mmol.) and the reaction mixture cooled to 0° C. Methanesulfonyl chloride (1.70 mL, 22.0 mmol) was added dropwise and the reaction stirred for 2 h. Water (100 mL) was then added to the reaction and pH of the aqueous layer adjusted to pH˜5 using aq. 2N HCl. The organics were separated and the aqueous layer was extracted into EtOAc (2×100 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo. A portion of the solid obtained (2.6 g) was dissolved in EtOH (166 mL), solid potassium hydroxide (2.82 g, 50.3 mmol) was added and the reaction heated at 50° C. After 2 h, the reaction mixture was cooled to RT, diluted with water (100 mL) and the pH adjusted to 5 using aq. 2N HCl. The organics were extracted into EtOAc (3×100 mL), dried (Na2SO4) and concentrated in vacuo to give 4 g crude of the desired product. A portion of the crude material (1 g) was purified by column chromatography on silica gel eluting with EtOAc:n-hexane (gradient elution from 10% to 40% v/v) to give Compound (1) (330 mg). ESI-MS m/z calculated for [M+H]+: 419.1. found: 419.1. 1H NMR (400 MHz, d6-Acetone) δ 7.79 (brs, 1H), 7.66 (s, 1H), 7.61 (brs, 1H), 7.56-7.51 (m, 2H), 7.49 (s, 1H), 7.46-7.41 (m, 2H), 3.02 (s, 3H), 2.81 (d, J=4.7 Hz, 3H), 2.11-2.01 (m, 1H), 0.96-0.90 (m, 2H), 0.66-0.59 (m, 2H).

Workup

  1. customThe organics were separated
  2. extractionthe aqueous layer was extracted into EtOAc (2×100 mL)
  3. dry with materialThe combined organics were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customA portion of the solid obtained (2.6 g)
  6. temperaturethe reaction heated at 50° C
  7. waitAfter 2 h
  8. temperaturethe reaction mixture was cooled to RT
  9. extractionThe organics were extracted into EtOAc (3×100 mL)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-71395bcf132b40ad8a4b904a58cf16f4
Source dataset
uspto-grants-2016_09
Patent number
US09447080B2

Reaction notes

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