1,2-Dichloroethane → N1-(3-fluoro-4-(2-(pyrrolidine-1-carbonyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamide

HRID 418583

Reaction equation

HRID 418583 reaction equation
[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]([N:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)=[O:17])[S:15][C:8]=23)=[C:4]([F:25])[CH:3]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[O:40]=[C:41]([NH:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[CH2:42][C:43](O)=[O:44]>CN(C=O)C.CCOC(C)=O>[F:25][C:4]1[CH:3]=[C:2]([NH:1][C:43](=[O:44])[CH2:42][C:41]([NH:46][C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)=[O:40])[CH:24]=[CH:23][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]([N:18]3[CH2:19][CH2:20][CH2:21][CH2:22]3)=[O:17])[S:15][C:8]=12

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 2565932-(Phenylcarbamoyl)acetic acidHCID 59424653(7-(4-Amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)(pyrrolidin-1-yl)methanone

Product 1

HCID 45488051N1-(3-fluoro-4-(2-(pyrrolidine-1-carbonyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamideYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 23 (100 mg, 0.28 mmol), HOBT (49 mg, 0.36 mmol) and EDC (80 mg, 0.41 mmol) in DMF (5 mL) was added 3-oxo-3-(phenylamino)propanoic acid (1) (65 mg, 0.36 mmol). The reaction mixture was stirred for 1 day and was diluted with EtOAc. The resultant solution was washed with water and brine, dried over anhydrous sodium sulfate and concentrated to provide a residue, which was purified by column chromatography (eluents MeOH—CH2Cl2, 2:98, 5:95) to produce a solid material, which after trituration with EtOAc/hexane afforded 5f as a white solid (74 mg, 51% yield). MS (m/z): 519.2 (M+H).

Workup

  1. washThe resultant solution was washed with water and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customto provide a residue, which
  5. customwas purified by column chromatography (eluents MeOH—CH2Cl2, 2:98, 5:95)
  6. customto produce a solid material, which after trituration with EtOAc/hexane

Sources & evidence

ORD record
ord-c8eff29c9c054fe7b6f9ebfea75ac6e0
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Linked notes

Loading…