Hydrochloric Acid → N-{[2-[(3-Fluoro-4'-nitro-4-biphenylyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine

HRID 1822392Notes

Reaction equation

HRID 1822392 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:14](=[O:15])[C:13]([C:16]([NH:18][CH2:19][C:20]([OH:22])=[O:21])=[O:17])=[C:12]([OH:23])[C:11]([CH:24]([CH3:26])[CH3:25])=[N:10]2)=[C:4]([F:27])[CH:3]=1.[N+:28]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)([O-:30])=[O:29].C(=O)([O-])[O-].[K+].[K+].Cl>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[F:27][C:4]1[CH:3]=[C:2]([C:34]2[CH:35]=[CH:36][C:31]([N+:28]([O-:30])=[O:29])=[CH:32][CH:33]=2)[CH:7]=[CH:6][C:5]=1[CH2:8][N:9]1[C:14](=[O:15])[C:13]([C:16]([NH:18][CH2:19][C:20]([OH:22])=[O:21])=[O:17])=[C:12]([OH:23])[C:11]([CH:24]([CH3:26])[CH3:25])=[N:10]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27735524-Nitrophenylboronic acidHCID 54747353N-{[2-[(4-Bromo-2-fluorophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine

Product 1

HCID 54747348N-{[2-[(3-Fluoro-4'-nitro-4-biphenylyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycineYield 40.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a 5 mL microwave tube was added N-{[2-[(4-bromo-2-fluorophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (example 46(b), 1 g, 2.261 mmol), 4-nitrobenzenboronic acid (0.377 g, 2.261 mmol), potassium carbonate (0.938 g, 6.78 mmol), tetrakis(triphenylphosphine)palladium (0) (0.078 g, 0.068 mmol), 1,4-Dioxane (5 ml) and Water (1.667 ml). The mixture was irradiated at 100° C. for 20 minutes. The reaction mixture was diluted with water (10 ml) and acidified with 1N HCl to give a off-white precipitate that was collected by filtration. The mixture of products was purified by HPLC chromatography (ODS silica, gradient 10-100% acetonitrile/water (0.1% TFA)) to afford the title compound (450 mg, 0.920 mmol, 40.7% yield). 1H NMR (400 MHz, DMSO-d6) d ppm 15.93 (s, 1H), 12.97 (br. s., 1H), 10.14 (t, J=5.68 Hz, 1H), 8.30 (td, J=9.16, 2.65, 2.34 Hz, 2H), 8.01 (td, J=9.16, 2.65, 2.34 Hz, 2H), 7.73 (dd, J=11.37, 1.77 Hz, 1H), 7.63 (dd, J=7.96, 1.89 Hz, 1H), 7.41 (t, J=7.96 Hz, 1H), 5.37 (s, 2H), 4.10 (d, J=5.56 Hz, 2H), 3.19 (sept, J=6.86 Hz, 1H), 1.19 (d, J=6.82 Hz, 6H). MS (ES+) m/e 485 [M+H]+.

Workup

  1. customThe mixture was irradiated at 100° C. for 20 minutes
  2. customto give a off-white precipitate that
  3. filtrationwas collected by filtration
  4. additionThe mixture of products
  5. customwas purified by HPLC chromatography (ODS silica, gradient 10-100% acetonitrile/water (0.1% TFA))

Sources & evidence

ORD record
ord-c6334acd9c2d4f09a9cf58ee148fb8b2
Source dataset
uspto-grants-2009_10
Patent number
US07608621B2

Reaction notes

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