Lithium Hydroxide → HCID 46841272, compound

HRID 1846327Notes

Reaction equation

HRID 1846327 reaction equation
[Li+].[OH-].CS([O:7][CH2:8][CH2:9][O:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([C:18]2[N:27]([C:28]3[CH:33]=[CH:32][C:31]([N:34](S(C)(=O)=O)[S:35]([CH3:38])(=[O:37])=[O:36])=[CH:30][CH:29]=3)[C:26](=[O:43])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=2)=[CH:13][C:12]=1[CH3:44])(=O)=O>O1CCOCC1.O.C([O-])(O)=O.[Na+]>[OH:7][CH2:8][CH2:9][O:10][C:11]1[C:12]([CH3:44])=[CH:13][C:14]([C:18]2[N:27]([C:28]3[CH:33]=[CH:32][C:31]([NH:34][S:35]([CH3:38])(=[O:36])=[O:37])=[CH:30][CH:29]=3)[C:26](=[O:43])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=2)=[CH:15][C:16]=1[CH3:17]

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 131732432HCID 131732432, compound

Product 1

HCID 46841272HCID 46841272, compoundYield 52.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

LiOH (0.100 g, 4.10 mmol) was added to a solution of 2-(2,6-dimethyl-4-(3-(4-(N-(methylsulfonyl)methylsulfonamido)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy)ethyl methanesulfonate (0.280 g, 0.44 mmol) in dioxane (20 mL) and H2O (20 mL), before heating at reflux temperature for 3.5 hours. The mixture was diluted with saturated NaHCO3, extracted with CH2Cl2, and concentrated in vacuo. 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 (0.110 g, 52%). 1H-NMR (300 MHz, DMSO-d6): δ 9.83 (s, 1H), 8.17 (dd, J=6.7, 1.1 Hz, 1H), 7.86-7.92 (m, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.52-7.65 (m, 1H), 7.27 (d, J=8.8 Hz, 2H), 7.13 (d, J=8.8 Hz, 2H), 7.01 (s, 2H), 4.83 (t, J=5.5 Hz, 1H), 3.56-3.69 (m, 4H), 2.92 (s, 3H), 2.09 (s, 6H). MS (APCI) m/z: 480 (M+H)+.

Workup

  1. temperaturebefore heating
  2. temperatureat reflux temperature for 3.5 hours
  3. extractionextracted with CH2Cl2
  4. concentrationconcentrated in vacuo
  5. customPurification
  6. washeluting with 10% to 90% CH3CN in H2O with 0.1% TFA
  7. customThe desired fractions were collected
  8. extractionextracted
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-7611fbaba602484c8f092e29cb540fcc
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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