Acetic Acid → 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{(methylsulfonyl)[3-(oxiran-2-yl)propyl]amino}-2H-indazole-3-carboxamide

HRID 2272268Notes

Reaction equation

HRID 2272268 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([C:17]([NH:19][CH3:20])=[O:18])=[C:15]3[C:10]([CH:11]=[C:12]([N:24]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:25][CH2:26][CH2:27][CH:28]=[CH2:29])[C:13]([CH:21]4[CH2:23][CH2:22]4)=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1.C(O)(=[O:36])C.C1C(=O)N(Br)C(=O)C1.[OH-].[Na+]>O1CCOCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([C:17]([NH:19][CH3:20])=[O:18])=[C:15]3[C:10]([CH:11]=[C:12]([N:24]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:25][CH2:26][CH2:27][CH:28]4[CH2:29][O:36]4)[C:13]([CH:21]4[CH2:23][CH2:22]4)=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 67184N-bromobutanimideHCID 866990012-(4-Chlorophenyl)-5-cyclopropyl-N-methyl-6-[(methylsulfonyl)(pent-4-en-1-yl)amino]-2H-indazole-3-carboxamide

Product 1

HCID 866990022-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{(methylsulfonyl)[3-(oxiran-2-yl)propyl]amino}-2H-indazole-3-carboxamideYield 118.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (i) (156 mg, 0.32 mmol) and acetic acid (37 μL, 0.64 mmol) in anhydrous 1,4-dioxane (15 mL) and water (20 mL) at 0° C. was added NBS (68 mg, 0.13 mmol) in a single portion. The reaction mixture was allowed to warm slowly to room temperature over 1 h 25 min whereupon aq. 1 M NaOH solution (3 mL) was added and the reaction followed LCMS analysis. After 30 min, the reaction mixture was diluted with water (10 mL), extracted with EtOAc (3×10 mL) and the combined organics then dried (MgSO4) and concentrated in vacuo to obtain (ii) (191 mg, >100%). The crude product was used without further purification in the next step. ESI-MS m/z calculated for [M+H]+ 503.2. found: 503.1.

Workup

  1. additionwas added
  2. extractionextracted with EtOAc (3×10 mL)
  3. dry with materialthe combined organics then dried (MgSO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-06f4d575f15b401ab33b65f5228eeecd
Source dataset
uspto-grants-2015_09
Patent number
US09120775B2

Reaction notes

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