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

HRID 612129Notes

Reaction equation

HRID 612129 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-9d8445711def4c7895d54e66a3d0dfe8
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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