Water → tert-butyl 5-methoxy-3-(1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridin-7-yl)-1H-indole-1-carboxylate

HRID 1628053노트

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HRID 1628053 반응식
I[C:2]1[N:14]([S:15]([C:18]2[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=2)(=[O:17])=[O:16])[C:5]2=[N:6][CH:7]=[C:8]3[CH:12]=[N:11][N:10]([CH3:13])[C:9]3=[C:4]2[CH:3]=1.[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH:31]=[C:30]2B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[Cs+].[Cs+].O>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH:31]=[C:30]2[C:2]1[N:14]([S:15]([C:18]2[CH:19]=[CH:20][C:21]([CH3:22])=[CH:23][CH:24]=2)(=[O:17])=[O:16])[C:5]2=[N:6][CH:7]=[C:8]3[CH:12]=[N:11][N:10]([CH3:13])[C:9]3=[C:4]2[CH:3]=1

참가 물질

8

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 53217218tert-Butyl 5-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylateHCID 580099867-Iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine

생성물 1

HCID 58382058tert-butyl 5-methoxy-3-(1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridin-7-yl)-1H-indole-1-carboxylate수율 100.4%

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

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온도
85 °C

실험 절차

A flask was charged with 7-iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.80 g, 1.76 mmol, Preparation #1), tert-butyl 5-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (0.792 g, 2.12 mmol, prepared using H from tert-butyl 3-bromo-5-methoxy-1H-indole-1-carboxylate (SynChem) with 4,4,5,5-tetramethyl-1,3,2-dioxaborolane), Cs2CO3 (1.44 g, 4.42 mmol), PdCl2(PPh3)2 (0.074 g, 0.106 mmol), water (2.6 mL) and 1,4-dioxane (8.0 mL). The mixture was heated to about 85° C. for about 2 h and then cooled to rt. The mixture was diluted with DCM (60 mL) and washed with water (30 mL). The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography eluting with a gradient of 0 to 20% EtOAc/DCM to afford tert-butyl 5-methoxy-3-(1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridin-7-yl)-1H-indole-1-carboxylate (1.01 g, 100%): LC/MS (Table 2, Method c) Rt=1.71 min; MS m/z 572 (M+H)+.

후처리

  1. temperaturecooled to rt
  2. washwashed with water (30 mL)
  3. dry with materialThe organic layer was dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by silica gel chromatography
  7. washeluting with a gradient of 0 to 20% EtOAc/DCM

출처 및 근거

ORD 기록
ord-b1fd7f994419495a9c502cebf110894b
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785639B2

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