Methanol → N1-(3-Fluoro-4-(2-(pyridin-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamide

HRID 2193684Notes

Reaction equation

HRID 2193684 reaction equation
[F:1][C:2]1[CH:23]=[C:22]([N+:24]([O-])=O)[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[S:13][C:6]=12.[Cl-].[NH4+:28].[CH3:29][OH:30]>O.[Fe]>[F:1][C:2]1[CH:23]=[C:22]([NH:24][C:5](=[O:4])[CH2:6][C:29]([NH:28][C:2]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:3]=2)=[O:30])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[S:13][C:6]=12

Participants

6

Reactant 3

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 58790194HCID 58790194, compound

Product 1

HCID 16041415N1-(3-Fluoro-4-(2-(pyridin-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamide

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Procedure

To a suspension of the 63 (660 mg, 1.80 mmol) in MeOH (15 ml) and water (3 ml) was added ammonium chloride (81 mg, 0.84 eq, 1.51 mmol) and Fe (907 mg, 9 eq, 16.2 mmol) and the reaction mixture was heated to reflux for 2 hours. The reaction mixture was cooled to RT, filtered through celite then concentrated. The mixture was partitioned between DCM/H2O and the DCM was collected, dried over Na2SO4, filtered and concentrated to produce the amine 64 which was used directly in the next step (607 mg, 100%). To a solution of the amine 64 (607 mg, 1.80 mmol) in dry DMF (˜7 ml) was added the acid 1 (644 mg, 2 eq, 3.6 mmol), HOBT (365 mg, 1.5 eq, 2.7 mmol) and EDC (690 mg, 2 eq, 3.6 mmol) and the reaction mixture was stirred at RT overnight. The reaction mixture was concentrated to dryness and partitioned between EtOAc and water, the organic phase was collected, dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the crude was purified by column chromatography (EtOAc) to afford title compound 62 as a white solid (150 mg, 17% yield). 1H NMR (DMSO-d6) δ (ppm): 10.57 (s, 1H), 10.20 (s, 1H), 8.70 (m, 2H), 8.55 (d, J=5.28 Hz, 1H), 8.37 (s, 1H), 7.89 (m, 3H), 7.60 (m, 2H), 7.58 (m, 2H), 7.30 (dt, J=1.96 and 7.43 Hz, 2H), 7.07 (m, 1H), 6.70 (dd, J=0.78 and 5.28 Hz, 1H), 3.51 (s, 2H). MS (m/z): 499.1 (M+H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. filtrationfiltered through celite
  4. concentrationthen concentrated
  5. customThe mixture was partitioned between DCM/H2O
  6. customthe DCM was collected
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-108a528835f54efdaa1f018b2a39886d
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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