Hydrochloric Acid → 4-[4'-(1,3-Benzothiazol-2-ylamino)-1,1'-biphenyl-4-yl]-2-(2-methoxyethyl)-4-oxobutanoic acid

HRID 9595

反応式

HRID 9595 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:26])[CH2:15][CH:16]([CH2:22][CH2:23][O:24][CH3:25])[C:17]([O:19]CC)=[O:18])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl[C:28]1[S:29][C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[N:32]=1.[OH-].[Na+].Cl>C(O)CCC.CO>[S:29]1[C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[N:32]=[C:28]1[NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14](=[O:26])[CH2:15][CH:16]([CH2:22][CH2:23][O:24][CH3:25])[C:17]([OH:19])=[O:18])=[CH:12][CH:13]=2)=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 119872-ChlorobenzothiazoleHCID 14798Sodium HydroxideHCID 21985739Ethyl 4-(4'-amino-1,1'-biphenyl-4-yl)-2-(2-methoxyethyl)-4-oxobutanoate

生成物 1

HCID 114425584-[4'-(1,3-Benzothiazol-2-ylamino)-1,1'-biphenyl-4-yl]-2-(2-methoxyethyl)-4-oxobutanoic acid収率 31%

試薬・触媒・溶媒 2

HCID 2631-Butanol溶媒HCID 887Methanol溶媒

反応条件

温度
90 °C

実験手順

To a solution of ethyl 4-(4′-amino-1,1′-biphenyl-4-yl)-2-(2-methoxyethyl)-4-oxobutanoate (75 mg, 0.21 mmol) in butanol (4 mL), 2-chloro-benzothiazole (43 mg, 0.25 mmol) was added and the reaction mixture was heated at 90° C. overnight. The solvent was removed by rotary evaporation, the residue was redissolved in DMF (1 mL), a solution of 1 N aqueous NaOH (0.63 mL, 0.63 mmol) was added, and the mixture was stirred at rt overnight. A solution of 1 N aqueous HCl (0.3 mL, 0.3 mmol) and methanol (5 mL) were added to the reaction mixture, and the crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford 4-[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]-2-(2-methoxyethyl)-4-oxobutanoic acid as a white solid (30 mg, 31%). 1H NMR (300 MHz, DMSO-d6) δ 8.05 (d, 2 H), 7.95 (d, 2 H), 7.70 (m, 5 H), 7.60 (d, 1 H), 7.30 (t, 1 H), 7.15 (t, 2 H), 3.35 (m, 2 H), 3.25 (s, 3 H), 3.20 (m, 2 H), 2.90 (m, 1 H), 1.95–1.75 (m, 2 H); LC-MS ret. time 3.29 min (method 2), m/z 461.15 (MH+).

後処理

  1. customThe solvent was removed by rotary evaporation
  2. dissolutionthe residue was redissolved in DMF (1 mL)
  3. customthe crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

出典と根拠

ORDレコード
ord-171e3503a70341fda8474b8f5df5840b
出典データセット
uspto-grants-2006_08
特許番号
US07091228B2

関連ノート

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