2-Methoxyethanol → HCID 25060730, compound

HRID 2244056Notes

Reaction equation

HRID 2244056 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][OH:5].[H-].[Na+].[NH2:8][C:9]1[C:18]2[C:13](=[C:14](F)[C:15]([N:19]3[C:27]4[CH2:26][C:25]([CH3:29])([CH3:28])[CH2:24][C:23](=[O:30])[C:22]=4[C:21]([CH3:31])=[CH:20]3)=[CH:16][CH:17]=2)[N:12]=[CH:11][N:10]=1>CN(C=O)C>[NH2:8][C:9]1[C:18]2[C:13](=[C:14]([O:5][CH2:4][CH2:3][O:2][CH3:1])[C:15]([N:19]3[C:27]4[CH2:26][C:25]([CH3:29])([CH3:28])[CH2:24][C:23](=[O:30])[C:22]=4[C:21]([CH3:31])=[CH:20]3)=[CH:16][CH:17]=2)[N:12]=[CH:11][N:10]=1

Participants

5

Reactant 3

HCID 80192-MethoxyethanolHCID 24758Sodium hydrideHCID 25060729HCID 25060729, compound

Product 1

HCID 25060730HCID 25060730, compoundYield 80.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a small microwave vial with a stir bar, 2-methoxyethanol (19.3 mg, 0.253 mmol) is dissolved in DMF (1 mL). To this solution is added sodium hydride (60% suspension in mineral oil, 10.13 mg, 0.2532 mmol) and the mixture is stirred at room temperature for 5 minutes and 1-(4-Amino-8-fluoro-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one (42.8 mg, 0.126 mmol) is added. The reaction is sealed and placed in the microwave reactor where it is heated to 150° C. for 30 minutes. The reaction is cooled, quenched by adding 5 mL sat. NH4Cl (aq) and extracted with CH2Cl2 (3×1 mL). The combined organics are purified by silica gel chromatography by two gradient runs on the same column, the first 0% to 100% ethyl acetate in hexanes and the second 0% to 50% methanol in ethyl acetate. This gives the desired 1-[4-Amino-8-(2-methoxy-ethoxy)-quinazolin-7-yl]-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one as a tan powder (40 mg, 80% yield) (LC/MS m/z=395 [M+H]+).

Workup

  1. customThe reaction is sealed
  2. temperatureis heated to 150° C. for 30 minutes
  3. temperatureThe reaction is cooled
  4. customquenched
  5. additionby adding 5 mL sat. NH4Cl (aq)
  6. extractionextracted with CH2Cl2 (3×1 mL)
  7. customThe combined organics are purified by silica gel chromatography by two gradient runs on the same column

Sources & evidence

ORD record
ord-61f1e2346086405ab9e4748c61f165a2
Source dataset
uspto-grants-2010_03
Patent number
US07678803B2

Reaction notes

Loading…