Tetrahydrofuran ethyl acetate → 5-[6-(4-Hydroxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]indole-1-carboxylic ethylamide

HRID 387786Notes

Reaction equation

HRID 387786 reaction equation
[CH2:1]([NH:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][C:16]3[C:17]4[CH:24]=[C:23]([C:25]5[CH:30]=[CH:29][C:28]([O:31]CC6C=CC=CC=6)=[CH:27][CH:26]=5)[N:22](COCC[Si](C)(C)C)[C:18]=4[N:19]=[CH:20][N:21]=3)=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)=[O:5])[CH3:2].O.C(=O)(O)O.C(OCC)(=O)C.O1CCCC1>FC(F)(F)C(O)=O.C1(SC)C=CC=CC=1>[CH2:1]([NH:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][C:16]3[C:17]4[CH:24]=[C:23]([C:25]5[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=5)[NH:22][C:18]=4[N:19]=[CH:20][N:21]=3)=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 21939870Tetrahydrofuran ethyl acetateHCID 21993411Carbonic acid--water (1/1)HCID 589313905-[6-(4-benzyloxyphenyl)-7-(2-trimethylsilanylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-indole-1-carboxylic ethylamide

Product 1

HCID 589311825-[6-(4-Hydroxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]indole-1-carboxylic ethylamideYield 25.6%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 7520ThioanisoleSolvent

Conditions

Temperature
52.5 °C

Procedure

After dissolving 30 mg of 5-[6-(4-benzyloxyphenyl)-7-(2-trimethylsilanylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]indole-1-carboxylic ethylamide in 1 ml of trifluoroacetic acid and 0.1 ml of thioanisole, the mixture was stirred at 50-55° C. The mixture was then returned to room temperature, saturated bicarbonate water was added to alkalinity, and liquid separation and extraction were performed with an ethyl acetate-tetrahydrofuran (5:1) mixed solvent. The organic layer was concentrated, 1 ml of tetrahydrofuran and 1 ml of 2N aqueous sodium hydroxide were added to the residue, and the mixture was stirred at room temperature for 5 minutes. After neutralization with 1N hydrochloric acid, liquid separation and extraction were performed with an ethyl acetate-tetrahydrofuran (5:1) mixed solvent. The organic layer was concentrated and the residue was subjected to silica gel column chromatography (hexane-ethyl acetate) to obtain 5 mg of the title compound.

Workup

  1. customwas then returned to room temperature
  2. additionmixed solvent
  3. concentrationThe organic layer was concentrated
  4. addition1 ml of tetrahydrofuran and 1 ml of 2N aqueous sodium hydroxide were added to the residue
  5. stirringthe mixture was stirred at room temperature for 5 minutes
  6. customAfter neutralization with 1N hydrochloric acid, liquid separation and extraction
  7. additionmixed solvent
  8. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-3581c14fa79144658b60ef3c77d0ac2d
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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