Bromopinacolone → 1-[1-(3,3-Dimethyl-2-oxobutyl)-6-methoxy-1H-indazol-3-yl]-2-methylprop-1-en-1-yl dimethyl phosphate

HRID 229454Notes

Reaction equation

HRID 229454 reaction equation
[P:1]([O:21][CH3:22])([O:19][CH3:20])([O:3][C:4]([C:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[NH:10][N:9]=1)=[C:5]([CH3:7])[CH3:6])=[O:2].Br[CH2:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27]>CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+]>[P:1]([O:21][CH3:22])([O:19][CH3:20])([O:3][C:4]([C:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[N:10]([CH2:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[N:9]=1)=[C:5]([CH3:7])[CH3:6])=[O:2]

Participants

5

Reactant 2

HCID 21642BromopinacoloneHCID 68852077HCID 68852077, compound

Product 1

HCID 115319381-[1-(3,3-Dimethyl-2-oxobutyl)-6-methoxy-1H-indazol-3-yl]-2-methylprop-1-en-1-yl dimethyl phosphate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 10796Cesium carbonateSolvent

Procedure

Dissolve 0.52 g 1-(6-methoxy-1H-indazol-3-yl)-2-methylprop-1-en-1-yl dimethyl phosphate from the Step B above in 10 mL dry DMF. Weigh in 0.626 g cesium carbonate. Add 0.315 g (0.237 mL) 1-bromo-3,3-dimethylbutan-2-one and stir the resulting mixture at room temperature for 2 hours and at 50° C. for one day. Remove half of the DMF under reduced pressure. Dilute the residue with 1:1 MeCN and water, and purify on RP-HPLC using 20-100% MeCN gradient without TFA to give the title compound as a colorless solid. The title compound recrystallizes from 1:1 EtOAc and hexanes. 1H NMR (CDCl3, 500 MHz) δ 7.70 (d, 9.0 Hz, 1H), 6.86 (dd, 2.0 & 8.7 Hz, 1H), 6.48 (d, 2.1 Hz, 1H), 5.33 (s, 2H), 3.87 (s, 3H), 3.57 (d, JP-H=11.4 Hz, 6H), 2.02 (d, JP-H=2.5 Hz, 3H), 1.83 (d, JP-H=3.4 Hz, 3H), 1.32 (s, 9H).

Workup

  1. waitat 50° C. for one day
  2. customRemove half of the DMF under reduced pressure
  3. additionDilute the residue with 1:1 MeCN and water
  4. custompurify on RP-HPLC

Sources & evidence

ORD record
ord-2244619387004fd88776c258ed8458ab
Source dataset
uspto-grants-2009_07
Patent number
US07563816B2

Reaction notes

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