HCID 59647525, compound → 3-Fluoro-4-(6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yloxy)aniline

HRID 2201896Notes

Reaction equation

HRID 2201896 reaction equation
[F:1][C:2]1[CH:30]=[C:29]([N+:31]([O-])=O)[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][CH:6]=1.[H][H]>[Pd].C(O)C.O>[F:1][C:2]1[CH:30]=[C:29]([NH2:31])[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][CH:6]=1

Participants

6

Reactant 2

HCID 59647525HCID 59647525, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 469280403-Fluoro-4-(6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yloxy)anilineYield 49.8%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A reactor containing 4-(2-fluoro-4-nitro-phenoxy)-6-methoxy-7-(3-morpholin-4-yl propoxy)quinoline (2.5 kg) and 10 percent palladium on carbon (50 percent water wet, 250 g) in a mixture of ethanol and water containing concentrated hydrochloric acid (1.5 L) was pressurized with hydrogen gas (approximately 40 psi). The mixture was stirred at ambient temperature. When the reaction was complete (typically 2 hours), as evidenced by in process HPLC analysis, the hydrogen was vented and the reactor inerted with argon. The reaction mixture was filtered through a bed of Celite® to remove the catalyst. Potassium carbonate was added to the filtrate until the pH of the solution was approximately 10. The resulting suspension was stirred at 20 to 25° C. for approximately 1 hour. The solids were collected by filtration, washed with water, and dried at 50 to 60° C. under reduced pressure to afford the title compound (1.164 kg). 1H NMR (400 MHz, DMSO-d6): δ 8.45 (d, 1H), 7.51 (s, 1H), 7.38 (s, 1H), 7.08 (t, 1H), 6.55 (dd, 1H), 6.46 (dd, 1H), 6.39 (dd, 1H), 5.51 (br. s, 2H), 4.19 (t, 2H), 3.94 (s, 3H), 3.59 (t, 4H), 2.47 (t, 2H), 2.39 (m, 4H), 1.98 (m, 2H). LC/MS Calcd for [M+H]+ 428.2. found 428.1.

Workup

  1. customtypically 2 hours
  2. filtrationThe reaction mixture was filtered through a bed of Celite®
  3. customto remove the catalyst
  4. additionPotassium carbonate was added to the filtrate until the pH of the solution
  5. stirringThe resulting suspension was stirred at 20 to 25° C. for approximately 1 hour
  6. filtrationThe solids were collected by filtration
  7. washwashed with water
  8. customdried at 50 to 60° C. under reduced pressure

Sources & evidence

ORD record
ord-82e937cc634646db82c4155a698f3103
Source dataset
uspto-grants-2016_06
Patent number
US09365516B2

Reaction notes

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