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

HRID 63539노트

반응식

HRID 63539 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매2회HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-714dd32b336f4c2ba1af0f1a76cac0fa
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447080B2

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