Phosphorus oxychloride → 10-chloro-1-methyl-3,8-dihydro-4H-[1,4]oxazepino[6,7-e]indole

HRID 2423198ノート

反応式

HRID 2423198 の反応式
[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][CH2:12][CH2:13][NH:14][C:15](=O)[CH3:16])[CH:9]=2)[N:4](S(C2C=CC=CC=2)(=O)=O)[CH:3]=1.O=P(Cl)(Cl)Cl>CCO.[OH-].[Na+].O.CC#N>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]3[O:11][CH2:12][CH2:13][N:14]=[C:15]([CH3:16])[C:9]3=2)[NH:4][CH:3]=1

参加物

7

反応物 2

HCID 24813Phosphorus oxychlorideHCID 67243669N-(2-{[3-chloro-1-(phenylsulfonyl)-1H-indol-5-yl]oxy}ethyl)acetamide2 回

生成物 1

HCID 13639364410-chloro-1-methyl-3,8-dihydro-4H-[1,4]oxazepino[6,7-e]indole収率 15.6%

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 14798Sodium Hydroxide溶媒

反応条件

温度
75 °C

実験手順

N-(2-{[3-chloro-1-(phenylsulfonyl)-1H-indol-5-yl]oxy}ethyl)acetamide (Intermediate 39, 1.07 g, 2.73 mmol, ca 80% pure) in EtOH (25 ml) and 2 M NaOH (5 ml) were mixed and heated at 75° C. for 1 hour. The reaction mixture was cooled, diluted with water and extracted with DCM. The organic phase was dried (MgSO4) and evaporated to give the crude material (0.287 g) as a colorless oil. The crude material (0.250 g, 0979 mmol) was dissolved in MeCN (20 ml) and POCl3 was added. The reaction mixture was heated at 120° C. for 15 minutes in a microwave heater and evaporated. The crude material was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN) to give the title compound (99.7 mg) as a white solid. MS m/z 235 [M+H]+.

後処理

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with DCM
  3. dry with materialThe organic phase was dried (MgSO4)
  4. customevaporated
  5. customto give the crude material (0.287 g) as a colorless oil
  6. temperatureThe reaction mixture was heated at 120° C. for 15 minutes in a microwave heater
  7. customevaporated
  8. customThe crude material was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN)

出典と根拠

ORDレコード
ord-24dfaefcb7384ff2925ba7c022b13fe6
出典データセット
uspto-grants-2011_06
特許番号
US07960374B2

反応ノート

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