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Hydrochloric Acid → 2'-{[5-{[(carboxymethyl)amino]carbonyl}-4-hydroxy-3-(1-methylethyl)-6-oxo-1(6H)-pyridazinyl]methyl}-4-biphenylcarboxylic acid

HRID 1822417
ノート
印刷プレビュー

反応式

HRID 1822417 の反応式
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.[C:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)([OH:29])=[O:28].C(=O)([O-])[O-].[K+].[K+].Cl>O1CCOCC1.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>[C:20]([CH2:19][NH:18][C:16]([C:13]1[C:14](=[O:15])[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]([C:27]([OH:29])=[O:28])=[CH:31][CH:32]=2)[N:10]=[C:11]([CH:24]([CH3:26])[CH3:25])[C:12]=1[OH:23])=[O:17])([OH:22])=[O:21]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 54739212N-{[2-[(2-Bromophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine

生成物 1

HCID 547391982'-{[5-{[(carboxymethyl)amino]carbonyl}-4-hydroxy-3-(1-methylethyl)-6-oxo-1(6H)-pyridazinyl]methyl}-4-biphenylcarboxylic acid
収率 36.2%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 312751,4-Dioxane溶媒

実験手順

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-carboxybenzeneboronic acid (29.3 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 (5 ml), acidified with 1N HCl (2 ml), and extracted with ethyl acetate (20 ml). The organic phase was dried over MgSO4, filtered, and solvents removed under reduced pressure. The crude residue was purified by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA)) to afford the title compound 2′-{[5-{[(carboxymethyl)amino]carbonyl}-4-hydroxy-3-(1-methylethyl)-6-oxo-1(6H)-pyridazinyl]methyl}-4-biphenylcarboxylic acid (non-preferred name) (30 mg, 0.064 mmol, 36.1% yield) as a white powder. 1H NMR (400 MHz, DMSO-d6) d ppm 15.82 (s, 1H), 12.99 (br. s., 2 H), 10.06 (t, J=5.68 Hz, 1H), 7.99 (d, J=8.34 Hz, 2H), 7.52 (d, J=8.34 Hz, 2 H), 7.38 (dt, J=4.36, 2.24 Hz, 2H), 7.25-7.32 (m, 1H), 7.17-7.24 (m, 1H), 5.26 (s, 2H), 4.06 (d, J=5.56 Hz, 2H), 3.11 (sept, J=6.82 Hz, 1H), 1.10 (d, J=6.82 Hz, 6H). MS (ES+) m/e 466 [M+H]+.

後処理

  1. customThe mixture was irradiated at 100° C. for 20 minutes
  2. extractionextracted with ethyl acetate (20 ml)
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. customsolvents removed under reduced pressure
  6. customThe crude residue was purified by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA))

出典と根拠

ORDレコード
ord-a0e0928cd66845e291d727b76691384b
出典データセット
uspto-grants-2009_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07608621B2

反応ノート

読み込み中…

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