Morpholine → N-[4-(3-bromoanilino)-3-cyano-7-methoxyquinolin-6-yl]-4-morpholin-4-ylbut-2-enamide

HRID 1935045Notes

Reaction equation

HRID 1935045 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:20][CH3:21])=[C:16]([NH2:19])[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:22]#[N:23])[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.Br[CH2:34]/[CH:35]=[CH:36]/[C:37](Cl)=[O:38].[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1.C(=O)(O)[O-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:20][CH3:21])=[C:16]([NH:19][C:37](=[O:38])[CH:36]=[CH:35][CH2:34][N:40]4[CH2:45][CH2:44][O:43][CH2:42][CH2:41]4)[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:22]#[N:23])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 98206456-Amino-4-[(3-bromophenyl)amino]-7-methoxy-quinoline-3-carbonitrileHCID 11263885(E)-4-Bromo-2-butenoyl Chloride

Product 1

HCID 54493686N-[4-(3-bromoanilino)-3-cyano-7-methoxyquinolin-6-yl]-4-morpholin-4-ylbut-2-enamideYield 38.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a mixture of 0.69 g (1.87 mmol) of 4-[(3-bromophenyl)amino]-7-methoxy-6-amino-3-quinolinecarbonitrile and 0.98 ml (5.6 mmol) of Hunig's base in 50 ml of dry THF at 0° C., with stirring, was added a THF solution containing 0.86 g (5 mmol) of 4-bromocrotonyl chloride dropwise. The mixture was stirred for a additional 0.5 hour and then was added to a solution of 4.89 ml (56 mmol) morpholine in 50 ml THF at 0° C. dropwise. The solution was stirred an additional 0.5 hour and then the mixture was poured into diluted sodium bicarbonate solution . The organic layer was separated and dried over sodium sulfate. The residue was chromatographed to give 0.38 g of grey solid: mass spectrum (electrospray, m/e): M+H 521.9 and 523.8.

Workup

  1. stirringThe mixture was stirred for a additional 0.5 hour
  2. stirringThe solution was stirred an additional 0.5 hour
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. customThe residue was chromatographed

Sources & evidence

ORD record
ord-a686f6b8ed7b462a9a1fd56345527de9
Source dataset
uspto-grants-2002_05
Patent number
US06384051B1

Reaction notes

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