Triethylamine → Methyl 7-(4-fluorophenyl)-3-(2-hydroxy-2-methylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazole-5-carboxylate

HRID 592330ノート

反応式

HRID 592330 の反応式
[NH2:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:6][C:5]([C:15]([O:17][CH3:18])=[O:16])=[CH:4][C:3]=1[NH:19][CH2:20][C:21]([OH:24])([CH3:23])[CH3:22].C(N(CC)CC)C.Cl[C:33](Cl)([O:35]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl.C(=O)(O)[O-].[Na+]>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:7]2[C:2]3[NH:1][C:33](=[O:35])[N:19]([CH2:20][C:21]([OH:24])([CH3:22])[CH3:23])[C:3]=3[CH:4]=[C:5]([C:15]([O:17][CH3:18])=[O:16])[CH:6]=2)=[CH:9][CH:10]=1

参加物

6

反応物 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 66693327Methy 6-amino-4'-fluoro-5-[(2-hydroxy-2-methylpropyl)amino]biphenyl-3-carboxylate

生成物 1

HCID 66690107Methyl 7-(4-fluorophenyl)-3-(2-hydroxy-2-methylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazole-5-carboxylate収率 83.4%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒4 回HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
30 °C

実験手順

To a solution of methy 6-amino-4′-fluoro-5-[(2-hydroxy-2-methylpropyl)amino]biphenyl-3-carboxylate (180 mg, 0.542 mmol) in dichloromethane (16.2 mL) was added triethylamine (0.091 mL, 0.650 mmol) followed by triphosgene (80.0 mg, 0.271 mmol) in dichloromethane (5.42 mL). Reaction heated at 30° C. for 4 h. Reaction was cooled, diluted with saturated sodium bicarbonate and dichloromethane. Adjusted aqueous layer to pH=14. Wash aqueous with dichloromethane (5×). Combined organics were dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% NOH) gave the title compound (81.0 mg): LC-MS [M+1]=359.2.

後処理

  1. customReaction
  2. customReaction
  3. temperaturewas cooled
  4. dry with materialCombined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% NOH)

出典と根拠

ORDレコード
ord-51326e9465ae4a59940cc7c37c580db5
出典データセット
uspto-grants-2016_01
特許番号
US09238647B2

反応ノート

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