Diisopropylethylamine → HCID 66584187, compound

HRID 1258447Notes

Reaction equation

HRID 1258447 reaction equation
Br.[F:2][CH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[Cl:9][C:10]1[CH:11]=[C:12]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:35][CH3:36])=[C:25]([NH:28][C:29](=[O:34])[CH:30]=[CH:31][CH2:32]Cl)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:13]=[CH:14][C:15]=1[F:16].CCN(C(C)C)C(C)C>C1COCC1.C(OCC)(=O)C>[Cl:9][C:10]1[CH:11]=[C:12]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:35][CH3:36])=[C:25]([NH:28][C:29](=[O:34])[CH:30]=[CH:31][CH2:32][N:6]4[CH2:7][CH2:8][CH:3]([F:2])[CH2:4][CH2:5]4)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:13]=[CH:14][C:15]=1[F:16]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 66584297HCID 66584297, compoundHCID 66584355HCID 66584355, compound

Product 1

HCID 66584187HCID 66584187, compoundYield 54.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

131 mg of 4-Fluoro-piperidine hydrobromide was added to 300 mg of 4-Chloro-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinazolin-6-yl]-amide and 0.37 ml of DIEA were dissolved in 5 ml THF stirred at 70° C. overnight. The mixture was then diluted with ethyl acetate, washed with water and brine and dried over Na2SO4. The resulting solids were flash chromatographed with 0-4% methanol in chloroform to give 189.4 mg of 4-(4-Fluoro-piperidin-1-yl)-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinazolin-6-yl]-amide.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. customchromatographed with 0-4% methanol in chloroform

Sources & evidence

ORD record
ord-1b6d3d2d36494486af4531ddb922bc83
Source dataset
uspto-grants-2013_06
Patent number
US08466165B2

Reaction notes

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