Potassium Carbonate → 4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[1-(N,N-dimethylcarbamoylmethyl)piperidin-3-yloxy]quinazoline

HRID 1948970Notes

Reaction equation

HRID 1948970 reaction equation
Cl[CH2:2][C:3]([N:5]([CH3:7])[CH3:6])=[O:4].Cl.Cl.[Cl:10][C:11]1[C:12]([F:37])=[C:13]([CH:34]=[CH:35][CH:36]=1)[NH:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:32][CH3:33])=[C:22]([O:25][CH:26]3[CH2:31][CH2:30][CH2:29][NH:28][CH2:27]3)[CH:23]=2)[N:18]=[CH:17][N:16]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:10][C:11]1[C:12]([F:37])=[C:13]([CH:34]=[CH:35][CH:36]=1)[NH:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:32][CH3:33])=[C:22]([O:25][CH:26]3[CH2:31][CH2:30][CH2:29][N:28]([CH2:2][C:3](=[O:4])[N:5]([CH3:7])[CH3:6])[CH2:27]3)[CH:23]=2)[N:18]=[CH:17][N:16]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 685224574-(3-Chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline dihydrochloride

Product 1

HCID 100057044-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[1-(N,N-dimethylcarbamoylmethyl)piperidin-3-yloxy]quinazolineYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Chloro-N,N-dimethylacetamide (105 mg) was added to a mixture of 4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline dihydrochloride (250 mg) and potassium carbonate (1.19 g) in DMF (5 ml). The mixture was stirred at room temperature for 30 mins, filtered and the solvent evaporated. Purification by flash column chromatography eluting with methylene chloride/methanol (96/4) gave a foam. This was triturated with diethyl ether and isohexane to give the title product as a white solid (105 mg); 1H NMR. Spectrum: (DMSO d6) 1.45 (m, 1H), 1.61 (m, 1H), 1.78 (m, 1H), 2.10 (m, 1H), 2.26 (m, 1H), 2.38 (m, 1H), 2.65-2.77 (m, 1H), 2.75 (s, 3H), 2.99 (s, 3H), 3.04 (m, 1H), 3.22 (s, 2H), 3.94 (s, 3H), 4.62 (m, 1H), 7.21 (s, 1H), 7.29 (m, 1H), 7.47-7.55 (m, 2H), 7.88 (s, 1H), 8.38 (s, 1H), 9.59 (s, 1H); Mass Spectrum: (M+H)+ 488.

Workup

  1. filtrationfiltered
  2. customthe solvent evaporated
  3. customPurification by flash column chromatography
  4. washeluting with methylene chloride/methanol (96/4)
  5. customgave a foam
  6. customThis was triturated with diethyl ether and isohexane

Sources & evidence

ORD record
ord-d248e976ad124abdb2408c3e37158ea0
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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