Cesium fluoride → 4-(6-Chloro-2,3-methylenedioxyanilino)-7-[(2r)-2,3-epoxypropoxy]-5-tetrahydropyran-4-yloxyquinazoline

HRID 1373326Notes

Reaction equation

HRID 1373326 reaction equation
[F-].[Cs+].CC1C=CC(S([O:13][CH2:14][C@@H:15]2[O:17][CH2:16]2)(=O)=O)=CC=1.[Cl:18][C:19]1[C:24]([NH:25][C:26]2[C:35]3[C:30](=[CH:31][C:32](F)=[CH:33][C:34]=3[O:36][CH:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[N:29]=[CH:28][N:27]=2)=[C:23]2[O:44][CH2:45][O:46][C:22]2=[CH:21][CH:20]=1>CN(C=O)C>[Cl:18][C:19]1[C:24]([NH:25][C:26]2[C:35]3[C:30](=[CH:31][C:32]([O:13][CH2:14][C@@H:15]4[O:17][CH2:16]4)=[CH:33][C:34]=3[O:36][CH:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[N:29]=[CH:28][N:27]=2)=[C:23]2[O:44][CH2:45][O:46][C:22]2=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 154187Glycidyl tosylate, (R)-HCID 11654626N-(5-Chlorobenzo[d][1,3]dioxol-4-yl)-7-fluoro-5-((tetrahydro-2H-pyran-4-yl)oxy)quinazolin-4-amine

Product 1

HCID 235755054-(6-Chloro-2,3-methylenedioxyanilino)-7-[(2r)-2,3-epoxypropoxy]-5-tetrahydropyran-4-yloxyquinazolineYield 76.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Caesium fluoride (0.46 g) and (2R)-(−)-glycidyl tosylate (0.275 g) were added in turn to a solution of 4-(6-chloro-2,3-methylenedioxyanilino)-7-fluoro-5-tetrahydropyran-4-yloxyquinazoline (0.416 g) in DMF (5 ml) and the reaction mixture was stirred and heated to 60° C. for 2 hours and to 70° C. for a further 1.5 hours. The mixture was evaporated and the residue was partitioned between ethyl acetate and a saturated aqueous sodium bicarbonate solution. The organic layer was washed with water and with brine, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using a 49:1 mixture of methylene chloride and methanol as eluent. There was thus obtained the title compound (0.36 g); NMR Spectrum: (CDCl3) 1.9–2.1 (m, 2H), 2.2–2.3 (m, 2H), 2.8 (m, 1H), 2.98 (m, 1H), 3.42 (m, 1H), 3.6–3.7 (m, 2H), 3.95–4.1 (m, 3H), 4.45 (m, 1H), 4.8 (m, 1H), 6.02 (s, 2H), 6.59 (m, 12H), 6.72 (d, 1H), 6.81 (d, 1H), 6.97 (d, 1H), 8.5 (s, 1H), 9.27 (s, 1H); Mass Spectrum: M+H+ 472 and 474.

Workup

  1. customThe mixture was evaporated
  2. customthe residue was partitioned between ethyl acetate
  3. washThe organic layer was washed with water and with brine
  4. dry with materialdried over magnesium sulphate
  5. customevaporated
  6. customThe residue was purified by column chromatography on silica using
  7. additiona 49:1 mixture of methylene chloride and methanol as eluent

Sources & evidence

ORD record
ord-5eb15af26658455b928dcb94e62e6d5b
Source dataset
uspto-grants-2007_01
Patent number
US07160891B2

Reaction notes

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