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

HRID 63539Notes

Reaction equation

HRID 63539 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. 1M 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-714dd32b336f4c2ba1af0f1a76cac0fa
Source dataset
uspto-grants-2016_09
Patent number
US09447080B2

Reaction notes

Loading…