Dichloromethane → 2-Chloro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzoic acid

HRID 1878781Notes

Reaction equation

HRID 1878781 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[CH:13][CH:12]=2)[N:7]=1.Br[C:25]1[CH:33]=[CH:32][C:28]([C:29]([OH:31])=[O:30])=[C:27]([Cl:34])[CH:26]=1.C([O-])([O-])=O.[Na+].[Na+].ClCCl>COCCOC.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:34][C:27]1[CH:26]=[C:25]([C:2]2[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=4)[N:14]=[CH:13][CH:12]=3)[N:7]=2)[CH:33]=[CH:32][C:28]=1[C:29]([OH:31])=[O:30]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 1088294-Bromo-2-chlorobenzoic acidHCID 598430126-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one

Product 1

HCID 598430422-Chloro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzoic acid

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A suspension of 6-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one (2290 mg, 6903 μmol), 4-bromo-2-chlorobenzoic acid (2766 mg, 13805 μmol), Na2CO3 (2 M, 13805 μl, 27611 μmol), and 1,1′-bis(diphenylphosphino)ferrocene]dichloride palladium(II) complex with dichloromethane (505 mg, 690 μmol) in DME (20 mL) was sparged with argon for 10 minutes then heated to reflux for 7 hours. The reaction was then partitioned between NaOH (1 M, 75 mL) and EtOAc (25 mL). The organic layer was discarded and the aqueous layer acidified to pH 4 with HCl (2M). The resulting orange precipitate was then collected by filtration and washed with water (50 mL). MS (ESI pos. ion) m/z: 452 (MH+); calc'd for C23H18ClN3O5: 451. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.86 (s, 3 H) 4.68 (s, 4 H) 6.94 (d, J=4.52 Hz, 1 H) 7.02 (d, J=9.03 Hz, 1 H) 7.09 (d, J=9.54 Hz, 1 H) 7.27 (s, 1 H) 7.60 (d, J=7.03 Hz, 1 H) 7.75 (d, J=7.03 Hz, 1 H) 7.81-7.98 (m, 2 H) 8.09 (d, J=9.54 Hz, 1 H) 8.62 (d, J=4.02 Hz, 1 H).

Workup

  1. customwas sparged with argon for 10 minutes
  2. temperaturethen heated
  3. temperatureto reflux for 7 hours
  4. customThe reaction was then partitioned between NaOH (1 M, 75 mL) and EtOAc (25 mL)
  5. filtrationThe resulting orange precipitate was then collected by filtration
  6. washwashed with water (50 mL)

Sources & evidence

ORD record
ord-70059fa5857d4f35a36a7b74d2027523
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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