Diethylamine → 4-Diethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide

HRID 612128Notes

Reaction equation

HRID 612128 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.[CH3:24][CH2:25][N:26]([CH:30]([CH3:32])C)[CH:27]([CH3:29])C.BrC/C=[CH:36]/[C:37](Cl)=[O:38].C(NCC)C.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:32][CH2:30][N:26]([CH2:25][CH3:24])[CH2:27][CH3:29])[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 8021DiethylamineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 98206456-Amino-4-[(3-bromophenyl)amino]-7-methoxy-quinoline-3-carbonitrileHCID 11263885(E)-4-Bromo-2-butenoyl Chloride

Product 1

HCID 542741594-Diethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amideYield 28.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a mixture of 0.5 g (1.36 mmol) of 4-[(3-bromophenyl)amino]-7-methoxy-6-amino-3-quinolinecarbonitrile and 0.48 ml (2.7 mmol) of Hunig's base in 50 ml of dry THF at 0° C., with stirring, was added a THF solution containing 0.50 g (2.7 mmol) of 4-bromo crotonyl chloride dropwise. The mixture was stirred for additional 0.5 hour after addition and then was added to a solution of 4.2 ml (40.8 mmol) diethyl amine in 50 ml of THF at 0° C. dropwise. The solution was stirred for an additional 0.5 hour. The mixture was poured into diluted sodium bicarbonate solution. The organic layer was separated and dried over sodium sulfate. Chromatography gave 0.2 g of white solid: mass spectrum (electrospray, m/e): M+H 508.1 and 510.8.

Workup

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

Sources & evidence

ORD record
ord-302e1a54cadd4bb2994f385cd5f8a185
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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