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

HRID 612135ノート

反応式

HRID 612135 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:23]#[N:24])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:25][CH2:26][N:27]([CH:31]([CH3:33])C)[CH:28]([CH3:30])C.BrC/C=[CH:37]/[C:38](Cl)=[O:39].[Na+].[Cl-].C(NCC)C.C(=O)(O)[O-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([NH:20][C:38](=[O:39])[CH:37]=[CH:33][CH2:31][N:27]([CH2:26][CH3:25])[CH2:28][CH3:30])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:23]#[N:24])[CH:5]=[CH:6][C:7]=1[F:8]

参加物

8

反応物 6

HCID 5234Sodium ChlorideHCID 8021DiethylamineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 11263885(E)-4-Bromo-2-butenoyl ChlorideHCID 224666136-Amino-4-[(3-bromo-4-fluorophenyl)amino]-7-methoxy-3-quinolinecarbonitrile

生成物 1

HCID 544873344Diethylamino-but-2-enoic acid [4(3-bromo-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide収率 38.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

実験手順

To a mixture of 0.77 g (1.98 mmol) of 4-[(3-bromo-4-fluorophenyl)amino]-7-methoxy-6-amino-quinoline-3-carbonitrile and 3.5 ml (20 mmol) of Hunig's base in 35 ml of dry THF at 0° C., with stirring, was added a THF solution containing 2.2 g (12 mmol) of 4-bromo crotonyl chloride dropwise. The mixture was stirred for additional 30 minutes at 0° C. 50 ml of saturated NaCl solution was added to the reaction mixture, then it was extracted with ethyl acetate. The ethyl acetate solution was dried over sodium sulfate and then was added to a solution of 3.1 ml (30 mmol) of diethyl amine in 5 ml of THF at 0° C. dropwise. The solution was stirred an additional hour at 0° C. and 30 minutes at room temperature. The mixture was poured into diluted sodium bicarbonate solution. The organic layer was dried over sodium sulfate and solvent was removed under vacuum. The residue was chromatographed to give 0.4 g off-white solid: mass spectrum (electrospray, m/e): M+H 525.9 and 527.9.

後処理

  1. stirringThe mixture was stirred for additional 30 minutes at 0° C
  2. extractionit was extracted with ethyl acetate
  3. dry with materialThe ethyl acetate solution was dried over sodium sulfate
  4. stirringThe solution was stirred an additional hour at 0° C. and 30 minutes at room temperature
  5. dry with materialThe organic layer was dried over sodium sulfate and solvent
  6. customwas removed under vacuum
  7. customThe residue was chromatographed

出典と根拠

ORDレコード
ord-e5aa12e2149946378af5e54c9e819eef
出典データセット
uspto-grants-1999_12
特許番号
US06002008

反応ノート

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