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 1628053Notes

Reaction equation

HRID 1628053 reaction equation
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

Participants

8

Reactant 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

Product 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-carboxylateYield 100.4%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-b1fd7f994419495a9c502cebf110894b
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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