Water → HCID 11386311, compound

HRID 1442989Notes

Reaction equation

HRID 1442989 reaction equation
Br[CH2:2][CH2:3][OH:4].C(=O)([O-])[O-].[K+].[K+].[Cl:11][C:12]1[CH:13]=[C:14]([CH:38]=[CH:39][C:40]=1[F:41])[NH:15][C:16]1[C:25]2[C:20](=[CH:21][C:22]([OH:37])=[CH:23][C:24]=2[O:26][CH2:27][C@H:28]2[CH2:32][CH2:31][CH2:30][N:29]2[C:33](=[O:36])[CH2:34][OH:35])[N:19]=[CH:18][N:17]=1.O>CN(C=O)C>[Cl:11][C:12]1[CH:13]=[C:14]([CH:38]=[CH:39][C:40]=1[F:41])[NH:15][C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:37][CH2:2][CH2:3][OH:4])=[CH:23][C:24]=2[O:26][CH2:27][C@H:28]2[CH2:32][CH2:31][CH2:30][N:29]2[C:33](=[O:36])[CH2:34][OH:35])[N:19]=[CH:18][N:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 108982-BromoethanolHCID 11430Potassium CarbonateHCID 136344269HCID 136344269, compound

Product 1

HCID 11386311HCID 11386311, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

2-Bromoethanol (51 μl) and potassium carbonate (86 mg) were added to a mixture of 4-[3-chloro-4-fluoroanilino]-5-{[(2R)-1-glycoloylpyrrolidin-2-yl]methoxy}-quinazolin-7-ol (70 mg) in DMF and the reaction mixture was heated at 70° C. for 16 hours. The reaction mixture was cooled to room temperature and then water (5 ml) was added to leave a white precipitate. The precipitate was filtered, washed with water and then purified by column chromatography using 2-5% methanol in DCM as eluent. The product was purified further by acidic reverse phase HPLC, and then the combined fractions were reduced to a third of the initial concentration, basified with sodium carbonate and extracted with ethyl acetate. The organic layer was dried (Na2SO4) and concentrated in vacuo to give the title compound as a white solid (35 mg, 45%); NMR Spectrum (DMSO-d6 at 373 K) 9.80 (br s, 1H), 8.40 (s, 1H), 8.15 (m, 1H), 7.65 (m, 1M, 7.33 (m, 1H), 6.80 (m, 2H), 4.60 (m, 1H), 4.50 (m, 1H), 4.30-4.10 (m, 4H), 4.0 (m, 2H), 3.75 (m, 2H), 3.60 (m, 1H), 3.50-3.37 (m, 2H), 2.10-1.85 (m, 4H); Mass spectrum MH+ 491.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customto leave a white precipitate
  3. filtrationThe precipitate was filtered
  4. washwashed with water
  5. custompurified by column chromatography
  6. customThe product was purified further by acidic reverse phase HPLC
  7. concentrationconcentration
  8. extractionextracted with ethyl acetate
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6d6a7785d6f34337a2d5328952772d2e
Source dataset
uspto-grants-2010_02
Patent number
US07659279B2

Reaction notes

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