N1-[3-Fluoro-4-[[6-methoxy-7-(phenylmethoxy)-4-quinolinyl]oxy]phenyl]-N2-(2-phenylethyl)ethanediamide → HCID 136168658, compound

HRID 455834Notes

Reaction equation

HRID 455834 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:39])[C:28]([NH:30][CH2:31][CH2:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[O:29])=[CH:22][C:21]=3[F:40])=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:41][CH3:42])C1C=CC=CC=1>CO.CN(C=O)C.ClCCl.C(OCC)(=O)C.C(O)(=O)C.[OH-].[Pd+2].[OH-]>[F:40][C:21]1[CH:22]=[C:23]([NH:26][C:27](=[O:39])[C:28]([NH:30][CH2:31][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[O:29])[CH:24]=[CH:25][C:20]=1[O:19][C:13]1[C:12]2[C:17](=[CH:18][C:9]([OH:8])=[C:10]([O:41][CH3:42])[CH:11]=2)[N:16]=[CH:15][CH:14]=1

Participants

8

Reactant 1

HCID 57810393N1-[3-Fluoro-4-[[6-methoxy-7-(phenylmethoxy)-4-quinolinyl]oxy]phenyl]-N2-(2-phenylethyl)ethanediamide

Product 1

HCID 136168658HCID 136168658, compoundYield 96.1%

Reagents, catalysts & solvents 6

HCID 9942167Palladium hydroxideCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-{4-[(7-benzyloxy-6-methoxyquinolin-4-yl)oxy]-3-fluorophenyl}-N′-(2-phenylethyl)ethanediamide (32 g, 56 mmol) in methanol (200 mL), DMF (100 mL), dichloromethane (100 mL), ethyl acetate (100 mL) and acetic acid (5 mL) was added palladium hydroxide (4.2 g) and the mixture was shaken on a Parr hydrogenator under a hydrogen pressure of 45 psi for 4 h. The resulting suspension was filtered through celite and the solid residue was washed with boiling dichloromethane (2 L) and acetone (2 L). The combined filtrates were evaporated to yield N-{3-fluoro-4-[(7-hydroxy-6-methoxyquinolin-4-yl)oxy]phenyl}-N′-(2-phenylethyl)ethanediamide as an off-white solid (25.6 g, 95%). 1H NMR (400 MHz, d6-DMSO): δ 11.06 (s, 1H), 10.25 (br s, 1H), 9.12 (t, 1H), 8.40 (d, 1H), 8.01 (dd, 1H), 7.50-7.44 (m, 2H), 7.31-7.23 (m, 6H), 6.39 (d, 1H), 3.95 (s, 3H), 2.85 (t, 2H), 2.50 (m, 2H); IR (cm−1): 1666, 1624, 1585, 1520, 1481, 1427, 1377, 1256, 1211, 1194, 1022, 880, 850, 839, 802, 750, 700; LC/MS (M+H=476).

Workup

  1. filtrationThe resulting suspension was filtered through celite
  2. washthe solid residue was washed with boiling dichloromethane (2 L) and acetone (2 L)
  3. customThe combined filtrates were evaporated

Sources & evidence

ORD record
ord-bf2ffedbe1a944ea9d01ba2f1ca0d660
Source dataset
uspto-grants-2013_07
Patent number
US08497284B2

Reaction notes

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