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

HRID 1822419
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HRID 1822419 반응식
[OH:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[N:6][N:5]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[CH:20][CH:19]=2)[C:4](=[O:27])[C:3]=1[C:28]([NH:30][CH2:31][C:32]([OH:34])=[O:33])=[O:29].[H][H]>[Pd].CO.C(OCC)(=O)C>[NH2:24][C:21]1[CH:20]=[CH:19][C:18]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[CH2:11][N:5]2[C:4](=[O:27])[C:3]([C:28]([NH:30][CH2:31][C:32]([OH:34])=[O:33])=[O:29])=[C:2]([OH:1])[C:7]([CH:8]([CH3:10])[CH3:9])=[N:6]2)=[CH:23][CH:22]=1
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반응물 2

HCID 54739201N-({5-hydroxy-6-(1-methylethyl)-2-[(4'-nitro-2-biphenylyl)methyl]-3-oxo-2,3-dihydro-4-pyridazinyl}carbonyl)glycineHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 54739193N-{[2-[(4'-amino-2-biphenylyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine수율 45.3%

시약·촉매·용매 3

HCID 23938Palladium촉매
HCID 887
Methanol
용매
HCID 8857Ethyl Acetate용매

실험 절차

To a Parr shaker flask was added N-({5-hydroxy-6-(1-methylethyl)-2-[(4′-nitro-2-biphenylyl)methyl]-3-oxo-2,3-dihydro-4-pyridazinyl}carbonyl)glycine (example 89, 65 mg, 0.139 mmol) and palladium on carbon (7.41 mg, 0.070 mmol) in Methanol (10 ml) and Ethyl acetate (2.500 ml) under a nitrogen atmosphere. The mixture was placed on a Parr shaker under 50 psi Hydrogen for 1 hour. The reaction mixture was filtered to remove the palladium on carbon followed by removal of the solvent by rotary evaporation and purification by HPLC chromatography (ODS silica, gradient 10-85% acetonitrile/water (0.1% TFA)) to afford the title compound N-{[2-[(4′-amino-2-biphenylyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (29 mg, 0.063 mmol, 45.3% yield) as a white powder. 1H NMR (400 MHz, DMSO-d6) d ppm 15.86 (s, 1H), 10.11 (t, J=5.56 Hz, 1H), 7.19-7.36 (m, 5 H), 7.05 (d, J=7.07 Hz, 1H), 6.93 (d, J=7.33 Hz, 2H), 5.25 (s, 2H), 4.08 (d, J=5.56 Hz, 2H), 3.16 (sept, J=6.82 Hz, 1H), 1.15 (d, J=6.82 Hz, 6H). MS (ES+) m/e 437 [M+H]+.

후처리

  1. filtrationThe reaction mixture was filtered
  2. customto remove the palladium on carbon
  3. customfollowed by removal of the solvent by rotary evaporation and purification by HPLC chromatography (ODS silica, gradient 10-85% acetonitrile/water (0.1% TFA))

출처 및 근거

ORD 기록
ord-4f3fe0dfd9b149458087379c66b927bd
출처 데이터셋
uspto-grants-2009_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07608621B2

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