1,2-Dichloroethane → (Z)-N1-(4-(2-(4-(Dimethylamino)but-1-enyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-methyl-N3-phenylmalonamide

HRID 2193737ノート

反応式

HRID 2193737 の反応式
[CH3:1][N:2]([CH3:25])[CH2:3][CH2:4]/[CH:5]=[CH:6]\[C:7]1[S:15][C:14]2[C:9](=[N:10][CH:11]=[CH:12][C:13]=2[O:16][C:17]2[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][C:18]=2[F:24])[CH:8]=1.[CH3:26][N:27]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28](=[O:33])[CH2:29][C:30](O)=[O:31].C(Cl)CCl>CN(C=O)C.CCOC(C)=O>[CH3:25][N:2]([CH3:1])[CH2:3][CH2:4]/[CH:5]=[CH:6]\[C:7]1[S:15][C:14]2[C:9](=[N:10][CH:11]=[CH:12][C:13]=2[O:16][C:17]2[CH:23]=[CH:22][C:20]([NH:21][C:30](=[O:31])[CH2:29][C:28]([N:27]([CH3:26])[C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)=[O:33])=[CH:19][C:18]=2[F:24])[CH:8]=1

参加物

6

反応物 3

HCID 111,2-Dichloroethane2 回HCID 3500563-(Methyl(phenyl)amino)-3-oxopropanoic acid2 回HCID 58790344(Z)-4-(2-(4-(Dimethylamino)but-1-enyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

生成物 1

HCID 58790146(Z)-N1-(4-(2-(4-(Dimethylamino)but-1-enyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-methyl-N3-phenylmalonamide収率 34.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of (Z)-4-(2-(4-(dimethylamino)but-1-enyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline (235) (69.1 mg, 0.193 mmol), 3-(methyl(phenyl)amino)-3-oxopropanoic acid 31 (46 mg, 0.26 mmol) (scheme 10), and EDC (45 mg, 0.24 mmol) in DMF (2.8 mL) was stirred overnight at room temperature. More 31 (45 mg, 0.26 mmol) and EDC (45 mg, 0.24 mmol) were added and the mixture stirred 6 h more. The mixture was diluted with EtOAc, washed with water, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was redissolved in MeOH and purified twice by preparative HPLC (gradient 40% to 95% MeOH in water, 45 min) giving title compound 231 (35 mg, 0.066 mmol, 34% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.32 (s, 1H), 8.48 (d, J=5.5 Hz, 1H), 7.80 (d, J=12.7 Hz, 1H), 7.54 (s, 1H), 7.5-7.3 (m, 7H), 6.78 (d, J=12.2 Hz, 1H), 6.62 (d, J=5.5 Hz, 1H), 5.92 (tt, J=7.2 Hz, J=4.5 Hz, 11.7 Hz, 1H), 3.21 (s, 5H), 2.59 (m, 2H), 2.42 (dd, 6.8 Hz, 7.4 Hz, 2H), 2.16 (s, 6H). MS (m/z): (M+1) 533.1 (100 N.

後処理

  1. washwashed with water
  2. dry with materialdried over anhydrous Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was redissolved in MeOH
  5. custompurified twice by preparative HPLC (gradient 40% to 95% MeOH in water, 45 min)

出典と根拠

ORDレコード
ord-6b1b9d914ed84e2381c76ade9fba9203
出典データセット
uspto-grants-2012_12
特許番号
US08329726B2

反応ノート

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