HCID 58902337, compound → HCID 58902314, compound

HRID 1640170Notes

Reaction equation

HRID 1640170 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:21]=[C:20]3[C:15]([CH:16]=[CH:17][C:18]([C:22]([NH:24][C:25]4[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27]([C:33]([F:36])([F:35])[F:34])[CH:26]=4)=[O:23])=[CH:19]3)=[CH:14][CH:13]=2)[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2]>[Ni].C1COCC1.N.CO>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:21]=[C:20]3[C:15]([CH:16]=[CH:17][C:18]([C:22]([NH:24][C:25]4[CH:30]=[CH:29][C:28]([CH2:31][NH2:32])=[C:27]([C:33]([F:36])([F:34])[F:35])[CH:26]=4)=[O:23])=[CH:19]3)=[CH:14][CH:13]=2)[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 1

HCID 58902337HCID 58902337, compound

Product 1

HCID 58902314HCID 58902314, compoundYield 27.6%

Reagents, catalysts & solvents 4

HCID 935NickelCatalyst2×HCID 222AmmoniaSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A slurry of 7-{[2-(acetylamino)pyridin-4-yl]oxy}-N-[4-cyano-3-(trifluoromethyl)-phenyl]-2-naphthamide (I-157) (163 mg, 0.33 mmol) and Raney Nickel (2800 slurry in water, 50% v/v, approx 8 mg) in THF (5 mL) and 7.0 M ammonia in MeOH (5 mL), was allowed to stir under an atmosphere of hydrogen for 18 h. After this time, additional Raney Nickel was added and hydrogenation continued for a further 18 h. The reaction mixture was filtered through Celite and washed with THF and MeOH. The filtrate was concentrated and purified by column chromatography. The product was dissolved in MeOH and 2M HCl in Et2O was added. The solvents were evaporated to give 7-{[2-(acetylamino)pyridin-4-yl]oxy}-N-[4-(aminomethyl)-3-(trifluoromethyl)phenyl]-2-naphthamide (I-151) as an off-white solid (45 mg, 23%). 1H NMR (400 MHz, d6-DMSO): δ 11.27 (s, 1H), 10.97 (s, 1H), 8.67 (s, 1H), 8.63 (br.s, 2H), 8.36 (d, 1H), 8.28 (d, 1H), 8.24-8.16 (m, 3H), 8.09-8.06 (m, 1H), 7.93 (d, 1H), 7.55 (dd, 1H), 7.45 (d, 1H), 6.96 (dd, 1H), 4.15-4.11 (m, 2H), and 2.08 (s, 3H). LCMS: (FA) ES+ 495.4.

Workup

  1. waithydrogenation continued for a further 18 h
  2. filtrationThe reaction mixture was filtered through Celite
  3. washwashed with THF and MeOH
  4. concentrationThe filtrate was concentrated
  5. custompurified by column chromatography
  6. dissolutionThe product was dissolved in MeOH
  7. addition2M HCl in Et2O was added
  8. customThe solvents were evaporated

Sources & evidence

ORD record
ord-bac60a40db3c4967a5e308e063344c11
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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