HCID 22050077, compound → HCID 22051162, compound

HRID 1867177Notes

Reaction equation

HRID 1867177 reaction equation
Br[C:2]1[C:3](=[O:33])[N:4]([CH2:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=2)[C:5]2[C:10]([C:11]=1[O:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=1[F:21])=[CH:9][CH:8]=[CH:7][CH:6]=2>CO.[Pd].CC([O-])=O.CC([O-])=O.[Pd+2]>[F:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=1[CH2:13][O:12][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=2)[C:3](=[O:33])[CH:2]=1

Participants

5

Reactant 1

HCID 22050077HCID 22050077, compound

Product 1

HCID 22051162HCID 22051162, compoundYield 51.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Procedure

In a 25 mL round bottom flask was added, at room temperature, a solution of methyl 4-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-2-oxoquinolin-1(2H)-yl]methyl}benzoate (step 2) (120 mg, 0.233 mmol) in MeOH (3.0 mL). Next, a combination of Pd on carbon (10% Pd, weight by weight 50% water, 100 mg, 0.047 mmol) and Pd(OAc)2 (15 mg, 0.067 mmol) was added to the reaction vessel that purged with argon and then fitted with a septum. The vessel was then equipped with a 2.0 L hydrogen balloon (c.a. 20 psi). The resulting suspension was allowed to stir of 12.0 hours and was then directly applied to SiO2 chromatography using ethyl acetate/hexanes (3:7) to furnish the desired title compound as a solid (52 mg, 51%). 1H NMR (300 MHz, CDCl3) δ 8.05-7.98 (m, 3H), 7.55 (app q, J=8.3 Hz, 1H), 7.48 (app t, J=7.5 Hz, 1H), 7.30 (d, J=8.0 Hz 2H), 7.19 (app q, J=8.5, 2H), 7.05-6.90 (m, 2H), 6.28 (s, 1II), 5.60 (s, 2H), 5.26 (s, 2H), 3.91 (s, 3H); LC/MS C-18 column, tr=3.71 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 436 (M+H). ES-HRMS m/z 436.1371 (M+H calcd for C25H20BrF2NO4 requires 436.1355).

Workup

  1. additionIn a 25 mL round bottom flask was added, at room temperature
  2. customthat purged with argon
  3. customfitted with a septum
  4. customThe vessel was then equipped with a 2.0 L hydrogen balloon (c.a. 20 psi)

Sources & evidence

ORD record
ord-656416c2b5014bbc81482597626e7465
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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