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 2193737노트

반응식

HRID 2193737 반응식
[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

참가 물질

6

반응물 3

HCID 111,2-Dichloroethane2회HCID 3500563-(Methyl(phenyl)amino)-3-oxopropanoic acid2회HCID 58790344(Z)-4-(2-(4-(Dimethylamino)but-1-enyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-6b1b9d914ed84e2381c76ade9fba9203
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329726B2

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