Trimethyl phosphite → HCID 68852077, compound

HRID 229453Notes

Reaction equation

HRID 229453 reaction equation
Br[C:2]([CH3:17])([CH3:16])[C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[NH:7][N:6]=1)=[O:4].[P:18]([O:23]C)([O:21][CH3:22])[O:19][CH3:20]>>[P:18]([O:21][CH3:22])([O:19][CH3:20])([O:4][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[NH:7][N:6]=1)=[C:2]([CH3:17])[CH3:16])=[O:23]

Participants

3

Reactant 2

HCID 8472Trimethyl phosphiteHCID 68852805HCID 68852805, compound

Product 1

HCID 68852077HCID 68852077, compound

Procedure

The title compound was prepared from 2-bromo-1-(6-methoxy-1H-indazol-3-yl)-2-methylpropan-1-one from the above by heating in excess trimethyl phosphite at 62° C. for 21 hours. Excess trimethyl phosphite was removed by vacuum distillation. The residue was purified on RP-HPLC using 10-90% MeCN gradient in water without TFA. Fractions containing the title compound were pooled, evaporated to dry, and recrystallized from ethyl acetate to give the title compound as colorless crystals. 1H NMR (CDCl3, 500 MHz) δ 11.41 (br s, 1NH), 7.63 (d, 9.0 Hz, 1H), 6.815 (dd, 2.2 & 8.8 Hz, 1H), 6.77 (d, 1.8 Hz, 1H), 3.83 (s, 3H), 3.65 (d, JP-H=11.2 Hz, 6H), 2.04 (d, JP-H=2.5 Hz, 3H), 1.81 (d, JP-H=3.5 Hz, 3H). LC-MS: 2.79 min. (m/Z=201.1, 327.0, 349.2).

Workup

  1. customExcess trimethyl phosphite was removed by vacuum distillation
  2. customThe residue was purified on RP-HPLC
  3. additionFractions containing the title compound
  4. customevaporated
  5. customto dry
  6. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-2fc297607344463ab4e3b986ef35daa8
Source dataset
uspto-grants-2009_07
Patent number
US07563816B2

Reaction notes

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