Methanol → HCID 58381984, compound

HRID 1628027Notes

Reaction equation

HRID 1628027 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:25]([S:26]([C:29]2[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=2)(=[O:28])=[O:27])[C:16]2=[N:17][CH:18]=[C:19]3[CH:23]=[N:22][N:21]([CH3:24])[C:20]3=[C:15]2[CH:14]=1.B(Br)(Br)Br.CO.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:12][N:8]1[C:9]2[C:5](=[CH:4][C:3]([OH:2])=[CH:11][CH:10]=2)[C:6]([C:13]2[N:25]([S:26]([C:29]3[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:16]3=[N:17][CH:18]=[C:19]4[CH:23]=[N:22][N:21]([CH3:24])[C:20]4=[C:15]3[CH:14]=2)=[CH:7]1

Participants

6

Reactant 4

HCID 887MethanolHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 58382425HCID 58382425, compound

Product 1

HCID 58381984HCID 58381984, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 7-(5-methoxy-1-methyl-1H-indol-3-yl)-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.22 g, 0.46 mmol, [WO2009/152133, Example #42]) in DCM (10 mL) was cooled to about 0° C. BBr3 (1.0 M in DCM, 1.39 mL, 1.39 mmol) was added dropwise. The mixture was stirred at rt for about 16 h. The mixture was cooled to about 0° C. and MeOH (0.5 mL) was added dropwise followed by a solution of saturated aqueous NaHCO3 (6 mL). The mixture was concentrated in vacuo and the residue was partitioned between EtOAc (2×75 mL) and saturated aqueous NaHCO3 (50 mL). The organic layer was isolated and washed with saturated aqueous NaHCO3 (50 mL), brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (12 g silica gel column, EtOAc/MeOH/Et3N 100:10:0 to 100:10:1) to give 1-methyl-3-(1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridin-7-yl)-1H-indol-5-ol (0.21 g, 99%): LC/MS (Table 2, Method a) Rt=2.10 min; MS m/z 472 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to about 0° C.
  2. concentrationThe mixture was concentrated in vacuo
  3. customthe residue was partitioned between EtOAc (2×75 mL) and saturated aqueous NaHCO3 (50 mL)
  4. customThe organic layer was isolated
  5. washwashed with saturated aqueous NaHCO3 (50 mL), brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (12 g silica gel column, EtOAc/MeOH/Et3N 100:10:0 to 100:10:1)

Sources & evidence

ORD record
ord-83c493c2e5cc457e8aef4c5d996da3ad
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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