Sodium Iodide → HCID 58382025, compound

HRID 1628121Notes

Reaction equation

HRID 1628121 reaction equation
[CH3:1][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(C2C=CC(C)=CC=2)(=O)=O)[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.[H-].[Na+].[Na+].[I-].[P:40]([O:52][CH2:53]Cl)([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41]>CN(C=O)C>[P:40]([O:52][CH2:53][N:25]1[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]=[C:13]1[C:6]1[C:5]2[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=2)[N:8]([CH3:12])[CH:7]=1)([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])([O:47][C:48]([CH3:49])([CH3:50])[CH3:51])=[O:41]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 11701630Di-tert-butyl (chloromethyl) phosphateHCID 58382425HCID 58382425, compound

Product 1

HCID 58382025HCID 58382025, compoundYield 29.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7-(5-Methoxy-1-methyl-1H-indol-3-yl)-1-methyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (1.00 g, 3.02 mmol [WO2009/152133, Example #42]) and NaH (60 wt % in mineral oil, 0.200 g, 5.00 mmol) were added to DMF (40 mL) then the mixture was stirred at rt for about 10 min. Then NaI (0.068 g, 0.453 mmol) and di-tert-butyl chloromethyl phosphate (1.60 g, 6.19 mmol, [Journal of Medicinal Chemistry (2008), 51(5), 1111-1114]) were added then the mixture was warmed to about 60° C. for about 45 min. The mixture was cooled to rt then concentrated under reduced pressure. The material was partitioned between water (50 mL) and EtOAc (50 mL). The organic layer was isolated and the aqueous layer was extracted with EtOAc (2×50 mL) then DCM (2×30 mL). The combined organics were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The material was purified using an 80 g silica column and eluting with EtOAc to give di-tert-butyl (7-(5-methoxy-1-methyl-1H-indol-3-yl)-1-methylpyrazolo[3,4-d]pyrrolo[2,3-b]pyridin-6(1H)-yl)methyl phosphate (0.486 g, 29%): LC/MS (Table 2, Method a) Rt=2.68 min; MS m/z 554 (M+H)+.

Workup

  1. temperaturethe mixture was warmed to about 60° C. for about 45 min
  2. temperatureThe mixture was cooled to rt
  3. concentrationthen concentrated under reduced pressure
  4. customThe material was partitioned between water (50 mL) and EtOAc (50 mL)
  5. customThe organic layer was isolated
  6. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  7. dry with materialThe combined organics were dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe material was purified
  11. washeluting with EtOAc

Sources & evidence

ORD record
ord-8573945c588c4f62844cc92b39fcccac
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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