3-(4-piperidyl)-1H-indole → N-(4-Fluoro-3-methoxy-benzyl)-4-(3-piperidin-1-yl-indole-1-sulfonyl)-benzamide Hydrochloride

HRID 1178990노트

반응식

HRID 1178990 반응식
[N:1]1([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:16][C:17]1[CH:36]=[CH:35][C:20]([CH2:21][NH:22][C:23]([C:25]2[CH:30]=[CH:29][C:28]([S:31]([Cl:34])(=[O:33])=[O:32])=[CH:27][CH:26]=2)=[O:24])=[CH:19][C:18]=1[O:37][CH3:38]>O1CCOCC1.CCOC(C)=O>[ClH:34].[F:16][C:17]1[CH:36]=[CH:35][C:20]([CH2:21][NH:22][C:23](=[O:24])[C:25]2[CH:26]=[CH:27][C:28]([S:31]([N:9]3[C:10]4[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=4)[C:7]([N:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)=[CH:8]3)(=[O:33])=[O:32])=[CH:29][CH:30]=2)=[CH:19][C:18]=1[O:37][CH3:38]

참가 물질

5

반응물 2

HCID 870923-(4-piperidyl)-1H-indoleHCID 589751944-(4-Fluoro-3-methoxy-benzylcarbamoyl)-benzenesulfonyl chloride

생성물 1

HCID 67023396N-(4-Fluoro-3-methoxy-benzyl)-4-(3-piperidin-1-yl-indole-1-sulfonyl)-benzamide Hydrochloride수율 50.1%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

Add KotBu (211 mg, 1.88 mmol) to a solution of 3-piperidin-1-yl-1H-indole (299 mg, 1.49 mmol) in dioxane (15 mL). Stir the yellow solution at RT for 30 min then treat with 4-(4-fluoro-3-methoxy-benzylcarbamoyl)-benzenesulfonyl chloride (560 mg, 1.56 mmol). Stir the solution at RT for an additional 2 h, then dilute with EtOAc (50 mL) and wash with satd NaHCO3 (25 mL). Remove the organic phase and extract the aqueous layer with additional EtOAc (50 mL). Combine the organic solutions, dry over Na2SO4, filter, and concentrate. Purify the crude material by flash chromatography (3×) using an oversized silica column and a gradient of 100% hexanes to 40% EtOAc/hexanes. Concentrate fractions containing pure material then redissolve in CH2Cl2 (10 mL) and treat with 4M HCl/dioxane (0.5 mL). Filter the off-white precipitate and dry under vacuum to give the title compound as a white powder (417 mg). MS (ES+) 522.1 (M+1)+, (ES−) 520.2 (M−1)−. 1H NMR (400 MHz, DMSO-d6): δ 9.19 (m, 1H), 8.03 (d, 2H, J=8.4), 7.97 (m, 1H), 7.95 (d, 2H, J=8.4), 7.61 (d, 1H, J=7.5), 7.37 (t, 1H, J=7.6), 7.26 (t, 2H, J=7.5), 7.06-7.13 (m, 2H), 6.81 (m, 1H), 6.12 (br s, 1H), 4.39 (d, 2H, J=5.7), 3.78 (s, 3H), 3.06 (s, 4H), 1.72 (s, 4H), 1.56 (s, 2H).

후처리

  1. stirringStir the solution at RT for an additional 2 h
  2. washwash with satd NaHCO3 (25 mL)
  3. customRemove the organic phase
  4. extractionextract the aqueous layer with additional EtOAc (50 mL)
  5. dry with materialCombine the organic solutions, dry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify the crude material by flash chromatography (3×)
  9. additionConcentrate fractions containing pure material
  10. dissolutionthen redissolve in CH2Cl2 (10 mL)
  11. additiontreat with 4M HCl/dioxane (0.5 mL)
  12. filtrationFilter the off-white precipitate
  13. customdry under vacuum

출처 및 근거

ORD 기록
ord-193f035a1c724e3bbc957d7d02880d8d
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07276516B2

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