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

HRID 1822415Notes

Reaction equation

HRID 1822415 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=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.[N+:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)([O-:29])=[O:28].C(=O)([O-])[O-].[K+].[K+].Cl>O1CCOCC1.O.CO.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>[OH:23][C:12]1[C:11]([CH:24]([CH3:26])[CH3:25])=[N:10][N:9]([CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[C:33]2[CH:34]=[CH:35][C:30]([N+:27]([O-:29])=[O:28])=[CH:31][CH:32]=2)[C:14](=[O:15])[C:13]=1[C:16]([NH:18][CH2:19][C:20]([OH:22])=[O:21])=[O:17]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27735524-Nitrophenylboronic acidHCID 54739212N-{[2-[(2-Bromophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine

Product 1

HCID 54739201N-({5-hydroxy-6-(1-methylethyl)-2-[(4'-nitro-2-biphenylyl)methyl]-3-oxo-2,3-dihydro-4-pyridazinyl}carbonyl)glycineYield 49.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a 5 ml microwave tube was added N-{[2-[(2-bromophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (example 78(b), 75 mg, 0.177 mmol), (4-nitrophenyl)boronic acid (29.5 mg, 0.177 mmol), potassium carbonate (73.3 mg, 0.530 mmol), and tetrakis(triphenylphosphine)palladium (0) (6.13 mg, 5.30 μmol) in 1,4-Dioxane (1.5 ml) and Water (0.500 ml). The mixture was irradiated at 100° C. for 20 minutes. The reaction mixture was diluted with water (4 ml), acidified with 1N HCl (1 ml), and diluted with methanol (2 ml) then filtered to remove any residue followed by purification by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA)) to afford the title compound N-({5-hydroxy-6-(1-methylethyl)-2-[(4′-nitro-2-biphenylyl)methyl]-3-oxo-2,3-dihydro-4-pyridazinyl}carbonyl)glycine (41 mg, 0.087 mmol, 49.2% yield) as a white powder. 1H NMR (400 MHz, DMSO-d6) d ppm 10.04 (t, J=5.43 Hz, 1H), 8.27 (ddd, J=9.03, 2.40, 2.21 Hz, 2 H), 7.69 (ddd, J=9.03, 2.40, 2.21 Hz, 2H), 7.37-7.48 (m, 2H), 7.20-7.34 (m, 2H), 5.27 (s, 2H), 4.03 (d, J=5.81 Hz, 2H), 3.10 (sept, J=6.86 Hz, 1H), 1.09 (d, J=6.82 Hz, 6 H). MS (ES+) m/e 467 [M+H]+.

Workup

  1. customThe mixture was irradiated at 100° C. for 20 minutes
  2. filtrationthen filtered
  3. customto remove any residue
  4. customfollowed by purification by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA))

Sources & evidence

ORD record
ord-3c377dac65ee4c2d8d501e23678f090d
Source dataset
uspto-grants-2009_10
Patent number
US07608621B2

Reaction notes

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