Hydrochloric Acid → HCID 56962687, compound

HRID 1037527Notes

Reaction equation

HRID 1037527 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]([Br: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].[OH-].[K+].Cl>C(Cl)Cl.C(O)C>[Br: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

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 675127246-amino-2-(4-bromophenyl)-5-cyclopropyl-N-methyl-2H-indazole-3-carboxamide

Product 1

HCID 56962687HCID 56962687, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a suspension of compound (ix) (320 mg, 0.83 mmol) in DCM (20 mL) was added DIPEA (0.43 mL, 2.49 mmol) followed by methanesulfonyl chloride (0.32 mL, 4.15 mmol) and the reaction mixture was stirred at RT for 3 h (monitored by LCMS). The mixture was diluted with DCM (20 mL), washed with saturated ammonium chloride (20 mL), brine (20 mL) and dried (MgSO4). The solvent was removed in vacuo to give a yellow solid. This material was taken up in ethanol (20 mL) and treated with powdered potassium hydroxide (210 mg, 3.80 mmol) and stirred for 5 min. The mixture was neutralized by addition of 1M aqueous hydrochloric acid and the resulting suspension was concentrated in vacuo to give an orange residue. The residue was taken up in DCM (20 mL), washed with water (20 mL), dried over MgSO4 and the solvent was removed in vacuo to give 2-(4-bromophenyl)-5-cyclopropyl-N-methyl-6-[(methylsulfonyl)amino]-2H-indazole-3-carboxamide (1) (300 mg, 86%) as yellow solid. ESI-MS m/z calculated for [M+H]+: 463.04/465.04; found: 463.05/465.05. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J=0.4 Hz, 1H), 7.68 (d, J=0.5 Hz, 1H), 7.65 (brd, J=8.8 Hz, 2H), 7.47 (d, J=8.8 Hz, 2H), 7.09 (s, 1H), 5.80 (brd, J=4.1 Hz, 1H), 3.13 (s, 3H), 3.00 (d, J=4.9 Hz, 3H), 1.80 (dddd, J=13.6, 8.1, 5.4, 1.3 Hz, 1H), 1.16-0.99 (m, 2H), 0.79-0.67 (m, 2H).

Workup

  1. washwashed with saturated ammonium chloride (20 mL), brine (20 mL)
  2. dry with materialdried (MgSO4)
  3. customThe solvent was removed in vacuo
  4. customto give a yellow solid
  5. stirringstirred for 5 min
  6. concentrationthe resulting suspension was concentrated in vacuo
  7. customto give an orange residue
  8. washwashed with water (20 mL)
  9. dry with materialdried over MgSO4
  10. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-410fc3d3248d41edaa5fa8edfe08046e
Source dataset
uspto-grants-2013_10
Patent number
US08546389B2

Reaction notes

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