1,2-Dichloroethane → N'-(4-(2-(2,2-Dimethylhydrazinecarbonyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide

HRID 418675Notes

Reaction equation

HRID 418675 reaction equation
N[C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]([NH:18][N:19]([CH3:21])[CH3:20])=[O:17])[S:15][C:8]=23)=[C:4]([F:24])[CH:3]=1.[CH3:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[NH:33][C:34](=[O:39])[CH2:35][C:36]([OH:38])=O.C(Cl)CCl.C[N:45](C=O)C>CCOC(C)=O>[CH3:20][N:19]([CH3:21])[NH:18][C:16]([C:14]1[S:15][C:8]2[C:9](=[N:10][CH:11]=[CH:12][C:7]=2[O:6][C:5]2[CH:22]=[CH:23][C:2]([N:33]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[O:26][CH3:25])[C:34](=[O:39])[CH2:35][C:36]([NH2:45])=[O:38])=[CH:3][C:4]=2[F:24])[CH:13]=1)=[O:17]

Participants

6

Reactant 4

HCID 111,2-Dichloroethane2×HCID 6228DimethylformamideHCID 12664594N-(2-Methoxy-phenyl)-malonamic acid2×HCID 587902227-(4-amino-2-fluorophenoxy)-N',N'-dimethylthieno[3,2-b]pyridine-2-carbohydrazide

Product 1

HCID 66649285N'-(4-(2-(2,2-Dimethylhydrazinecarbonyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamideYield 67%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 7-(4-amino-2-fluorophenoxy)-N′,N′-dimethylthieno[3,2-b]pyridine-2-carbohydrazide 239 (200 mg, 0.578 mmol), 3-(2-methoxyphenylamino)-3-oxopropanoic acid 27 (195 mg, 0.693 mmol), and EDC (230 mg, 0.693 mmol) in DMF (8.3 mL) was stirred overnight at room temperature. More 27 (195 mg, 0.693 mmol) and EDC (230 mg, 0.693 mmol) were added and the mixture stirred 6 h more. The crude was diluted with EtOAc, extracted with water, over with anhydrous Na2SO4, and concentrated under reduced pressure. The residue was re dissolved in MeOH and purified twice by flash chromatography (DCM/MeOH 9:1) affording 236 (207 mg, 0.385 mmol, 67% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.60 (s, 1H), 9.94 (s, 0.5H), 9.63 (s, 1H), 9.49 (s, 0.5H), 8.57 (dd, J=5.5 Hz, J=7.2 Hz, 1H), 8.26 (m, 1H), 8.07 (d, J=7.4 Hz, 1H), 7.88 (d, J=12.9 Hz, 1H), 7.54-7.43 (m, 2H), 7.07 (m, 2H), 6.91 (m, 1H), 6.73 (m, 1H), 3.86 (s, 3H), 3.65 (s, 2H), 2.63 (s, 3H), 2.61 (s, 3H). MS (m/z): (M+1) 538.0 (100%).

Workup

  1. extractionextracted with water, over with anhydrous Na2SO4
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was re dissolved in MeOH
  4. custompurified twice by flash chromatography (DCM/MeOH 9:1)

Sources & evidence

ORD record
ord-71b0c3bcae564d468196cbbd766c5524
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

Loading…