Methanesulfonyl chloride → HCID 46842155, compound

HRID 1846358Notes

Reaction equation

HRID 1846358 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=[C:14]2[C:24]2[CH:25]=[N:26][C:27]([CH3:30])=[CH:28][CH:29]=2)=[CH:9][CH:8]=1.O[Li].O>C(Cl)Cl.O1CCOCC1.O>[CH3:30][C:27]1[N:26]=[CH:25][C:24]([C:14]2[N:13]([C:10]3[CH:9]=[CH:8][C:7]([NH:6][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:12][CH:11]=3)[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)=[CH:29][CH:28]=1

Participants

7

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 168937Lithium hydroxide, monohydrateHCID 67454686HCID 67454686, compound

Product 1

HCID 46842155HCID 46842155, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Methanesulfonyl chloride (0.026 mL, 0.33 mmol) was added to a mixture of 3-(4-aminophenyl)-2-(6-methylpyridin-3-yl)quinazolin-4(3H)-one (0.11 g, 0.33 mmol) and TEA (0.093 mL, 0.67 mmol) in CH2Cl2 (5 mL). The mixture was stirred for 2 hours and concentrated in vacuo. The residue was redissolved in 1:1 dioxane and H2O (5 mL) and LiOH.H2O (0.050 g, 1.2 mmol) was added. The mixture was stirred at room temperature for 20 minutes, then extracted with EtOAc. The organics were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification was conducted by flash chromatography on silica gel, eluting with 10% to 80% of 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2, followed by further purification by reverse-phase chromatography, eluting with 10% to 50% CH3CN in H2O with 0.1% TFA. The desired fractions were basified and extracted to afford the title compound as a white solid (0.075 g, 56%). 1H-NMR (300 MHz, DMSO-d6): δ9.91 (s, 1H), 8.43 (s, 1H), 8.20 (d, J=8.0 Hz, 1H), 7.85-7.98 (m, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.54-7.69 (m, 2H), 7.33 (d, J=8.7 Hz, 2H), 7.05-7.22 (m, 3H), 2.97 (s, 3H), 2.39 (s, 3H). MS (APCI) m/z: 407 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. additionwas added
  3. stirringThe mixture was stirred at room temperature for 20 minutes
  4. extractionextracted with EtOAc
  5. washThe organics were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification
  10. washeluting with 10% to 80% of 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2
  11. customfollowed by further purification by reverse-phase chromatography
  12. washeluting with 10% to 50% CH3CN in H2O with 0.1% TFA
  13. extractionextracted

Sources & evidence

ORD record
ord-5fb691a1bfd944ff892c503ff978ee61
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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