2-Methyl-2-butene → 6-chloro-5-{4-[2-(morpholin-4-yl)-2-oxoethyl]phenyl}-1H-indole-3-carboxylic acid

HRID 1054752

反応式

HRID 1054752 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:20]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[O:21])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:34].[Na+].O.O.OP([O-])(O)=O.[Na+]>C(#N)C.C(O)(C)(C)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:34])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[CH:15][C:16]([CH2:19][C:20]([N:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)=[O:21])=[CH:17][CH:18]=1

参加物

8

反応物 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23673460Sodium Phosphate, Monobasic, DihydrateHCID 866987456-chloro-5-{4-[2-(morpholin-4-yl)-2-oxoethyl]phenyl}-1H-indole-3-carbaldehyde

生成物 1

HCID 866987466-chloro-5-{4-[2-(morpholin-4-yl)-2-oxoethyl]phenyl}-1H-indole-3-carboxylic acid収率 28%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 6386tert-Butanol溶媒

反応条件

温度
0 °C

実験手順

To a solution of 6-chloro-5-{4-[2-(morpholin-4-yl)-2-oxoethyl]phenyl}-1H-indole-3-carbaldehyde (249 mg, 0.650 mmol) in acetonitrile (6 mL) and tert-butanol (6 mL) was added 2-methyl-2-butene (4 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (880 mg, 13.1 mmol) and sodium phosphate monobasic dihydrate (2030 mg, 13.01 mmol) in water (3 mL) via addition funnel. The icebath was removed and the mixture was allowed to warm to room temperature. The reaction mixture was stirred at room temperature for 18 hours. The reaction was quenched with aqueous sodium sulfite, concentrated in vacuo and extracted with ethyl acetate (4×25 mL). The combined organic phases were washed with brine (20 mL), dried and concentrated in vacuo. The crude product was purified by prep-HPLC (Column: Phenomenex Synergi C18 150*30 mm*4 μm; Mobile phase: from 38% MeCN in water (0.225% FA) to 58% MeCN in water (0.225% FA); Wavelength: 220 nm) to afford the title compound (65 mg, 28% yield) as a white solid. MS (ES+) 399.0 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.03 (s, 1H), 8.01 (s, 1H), 7.59 (s, 1H), 7.43 (d, 2H), 7.34 (d, 2H), 3.87 (s, 2H), 3.65 (m, 4H), 3.52 (m, 2H), 3.55 (m, 2H).

後処理

  1. customThe icebath was removed
  2. temperatureto warm to room temperature
  3. customThe reaction was quenched with aqueous sodium sulfite
  4. concentrationconcentrated in vacuo
  5. extractionextracted with ethyl acetate (4×25 mL)
  6. washThe combined organic phases were washed with brine (20 mL)
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by prep-HPLC (Column: Phenomenex Synergi C18 150*30 mm*4 μm; Mobile phase: from 38% MeCN in water (0.225% FA) to 58% MeCN in water (0.225% FA); Wavelength: 220 nm)

出典と根拠

ORDレコード
ord-d3d764d534b64433b6742ba089c3ecc5
出典データセット
uspto-grants-2016_07
特許番号
US09394285B2

関連ノート

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