Diisopropylethylamine → HCID 11341301, compound

HRID 1879951Notes

Reaction equation

HRID 1879951 reaction equation
[N:1]1([C:7](Cl)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[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][NH:29][CH2:28][CH2:27]3)[CH:23]=2)[N:18]=[CH:17][N:16]=1.C(N(C(C)C)CC)(C)C>ClCCl>[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][N:29]([C:7]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[O:8])[CH2:28][CH2:27]3)[CH:23]=2)[N:18]=[CH:17][N:16]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 848104-Morpholinecarbonyl chlorideHCID 10408840N-(3-chloro-2-fluorophenyl)-7-methoxy-6-(piperidin-4-yloxy)quinazolin-4-amine

Product 1

HCID 11341301HCID 11341301, compoundYield 64.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

4-Morpholinylcarbonyl chloride (35 μl, 0.3 mmol) was added dropwise to a ice-cooled mixture of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline (120 mg, 0.3 mmol) and diisopropylethylamine (63 μl, 0.36 mmol) in dichloromethane (5 ml). At the end of the addition, the mixture was stirred at room temperature for 18 hours. The mixture was diluted with dichloromethane, washed with water and brine and dried over magnesium sulfate. After evaporation of the solvents under vacuum, the residue was purified by chromatography on silica gel (eluant: 1% to 2% 7N methanolic ammonia in dichloromethane) to give the title compound as a white solid (100 mg, 64%).

Workup

  1. temperaturecooled
  2. additionAt the end of the addition
  3. washwashed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. customAfter evaporation of the solvents under vacuum
  6. customthe residue was purified by chromatography on silica gel (eluant: 1% to 2% 7N methanolic ammonia in dichloromethane)

Sources & evidence

ORD record
ord-7b26cc21d7f840d1857d976c0206808c
Source dataset
uspto-grants-2012_11
Patent number
US08318752B2

Reaction notes

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