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Dimethylformamide → 6-chloro-3-cyano-N5-(1-cyanocyclopropyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

HRID 514270
ノート
印刷プレビュー

反応式

HRID 514270 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:13]([NH:15][CH:16]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:17]([F:20])([F:19])[F:18])=[O:14])[N:8]2[CH2:11][CH3:12])=[CH:4][C:3]=1[C:31]([NH:33][C:34]1([C:37]#[N:38])[CH2:36][CH2:35]1)=[O:32].ClS([N:43]=[C:44]=O)(=O)=O.CN(C)C=O>C(#N)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:44]#[N:43])=[C:7]([C:13]([NH:15][CH:16]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:28])[F:29])[CH:22]=3)[C:17]([F:18])([F:20])[F:19])=[O:14])[N:8]2[CH2:11][CH3:12])=[CH:4][C:3]=1[C:31]([NH:33][C:34]1([C:37]#[N:38])[CH2:35][CH2:36]1)=[O:32]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 6228Dimethylformamide2 回HCID 70918Chlorosulfonyl isocyanate2 回HCID 601689226-chloro-N5-(1-cyanocyclopropyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

生成物 1

HCID 867139886-chloro-3-cyano-N5-(1-cyanocyclopropyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide収率 5.7%

試薬・触媒・溶媒

1
HCID 6342Acetonitrile溶媒

反応条件

温度
0 °C

実験手順

6-Chloro-N5-(1-cyanocyclopropyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide (0.100 g, 0.18 mmol) is initially charged in dry acetonitrile (2 ml) under argon and cooled to 0° C., and chlorosulphonyl isocyanate (0.028 g, 0.19 mmol) is added dropwise. After 30 min, N,N-dimethylformamide (0.015 g, 0.19 mmol) is added and the mixture is stirred at 0° C. for a further 30 min and at room temperature overnight. Then the mixture is cooled again to 0° C. and chlorosulphonyl isocyanate (0.028 g, 0.19 mmol) is added dropwise, N,N-dimethylformamide (0.015 g, 0.19 mmol) is added after 30 min, and the mixture is stirred at room temperature for a further 48 h. The reaction mixture is then concentrated under reduced pressure, and the residue is admixed with sodium hydrogencarbonate and extracted with dichloromethane. The organic phase is dried with sodium sulphate, filtered and concentrated under reduced pressure. The residue is purified by means of preparative HPLC (Kromasil100, C18 250×20; eluent: acetonitrile in water, gradient: 10-100%) to obtain 0.006 g (5% of theory) of 6-chloro-3-cyano-N5-(1-cyanocyclopropyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide.

後処理

  1. temperatureThen the mixture is cooled again to 0° C.
  2. stirringthe mixture is stirred at room temperature for a further 48 h
  3. concentrationThe reaction mixture is then concentrated under reduced pressure
  4. extractionextracted with dichloromethane
  5. dry with materialThe organic phase is dried with sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by means of preparative HPLC (Kromasil100, C18 250×20

出典と根拠

ORDレコード
ord-5d2b872b947048b4a4060635975d8e78
出典データセット
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09107411B2

反応ノート

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