Methyl formate → HCID 46841270, compound

HRID 1846324Notes

Reaction equation

HRID 1846324 reaction equation
[CH:1](OC)=[O:2].[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=[C:13]2[C:23]2[CH:28]=[C:27]([CH3:29])[C:26]([O:30][CH2:31][CH2:32][OH:33])=[C:25]([CH3:34])[CH:24]=2)=[CH:8][CH:7]=1>CCO>[OH:33][CH2:32][CH2:31][O:30][C:26]1[C:25]([CH3:34])=[CH:24][C:23]([C:13]2[N:12]([C:9]3[CH:10]=[CH:11][C:6]([NH:5][CH:1]=[O:2])=[CH:7][CH:8]=3)[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=2)=[CH:28][C:27]=1[CH3:29]

Participants

4

Reactant 2

HCID 7865Methyl formate2×HCID 46841271HCID 46841271, compound

Product 1

HCID 46841270HCID 46841270, compoundYield 33.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methyl formate (10 mL, 162 mmol) was added to a solution of 3-(4-aminophenyl)-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one (0.200 g, 0.50 mmol) in EtOH (10 mL) and heated at reflux. More methyl formate (5 mL, 81 mmol) was added and the mixture was heated at reflux for 2 more days, before being concentrated in vacuo and purification by flash chromatography on silica gel eluting with 2% to 8% MeOH in CH2Cl2. Further purification was effected by reverse phase chromatography eluting with 10% to 90% CH3CN in H2O with 0.1% TFA. The desired fractions were collected, basified, extracted, and concentrated, to afford the title compound as a white solid (0.072 g, 33%). 1H-NMR (300 MHz, DMSO-d6, mixture of rotamers): δ 10.24 (s, 0.8H), 10.18 (m, 0.2H), 8.72-8.87 (m, 0.2H), 8.25 (d, J=1.7 Hz, 0.8H), 8.18 (dd, J=6.9, 1.1 Hz, 1H), 7.83-7.96 (m, 1H), 7.73 (d, J=8.0 Hz, 1H), 7.51-7.59 (m, 2.5H), 7.24 (d, J=8.7 Hz, 2H), 7.11-7.19 (m, 0.5H), 7.03 (s, 2H), 4.81 (t, J=5.4 Hz, 1H), 3.63-3.71 (m, 4H), 2.09 (s, 6H). MS (APCI) m/z: 430 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureat reflux
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 2 more days
  5. concentrationbefore being concentrated in vacuo and purification by flash chromatography on silica gel eluting with 2% to 8% MeOH in CH2Cl2
  6. customFurther purification
  7. washeluting with 10% to 90% CH3CN in H2O with 0.1% TFA
  8. customThe desired fractions were collected
  9. extractionextracted
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-82f15a006f9e4eff9c02ddda7a969ac0
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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