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Potassium Carbonate → Methyl 3-{[3-[[(5-chloro-2-thienyl)sulfonyl]({[2-(trimethylsilyl)ethyl]oxy}methyl)amino]-4-(methyloxy)-1H-indazol-1-yl]methyl}benzoate

HRID 1874676
ノート
印刷プレビュー

反応式

HRID 1874676 の反応式
[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]([C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][C:26]=3[O:28][CH3:29])[NH:21][N:20]=2)[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])(=[O:9])=[O:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:37][C:38]1[CH:39]=[C:40]([CH:45]=[CH:46][CH:47]=1)[C:41]([O:43][CH3:44])=[O:42]>CN(C=O)C.C(Cl)Cl.O>[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:16])[CH3:17])[C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][C:26]=3[O:28][CH3:29])[N:21]([CH2:37][C:38]3[CH:39]=[C:40]([CH:45]=[CH:46][CH:47]=3)[C:41]([O:43][CH3:44])=[O:42])[N:20]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1
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

7

反応物 3

HCID 11430Potassium CarbonateHCID 517981Methyl 3-(bromomethyl)benzoateHCID 580544435-chloro-N-[4-(methyloxy)-1H-indazol-3-yl]-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)-2-thiophenesulfonamide

生成物 1

HCID 58054540Methyl 3-{[3-[[(5-chloro-2-thienyl)sulfonyl]({[2-(trimethylsilyl)ethyl]oxy}methyl)amino]-4-(methyloxy)-1H-indazol-1-yl]methyl}benzoate収率 44%

試薬・触媒・溶媒 3

HCID 962
Water
溶媒
HCID 6228Dimethylformamide溶媒
HCID 6344Dichloromethane溶媒

反応条件

温度
50 °C

実験手順

A solution of 5-chloro-N-[4-(methyloxy)-1H-indazol-3-yl]-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)-2-thiophenesulfonamide (for a preparation see Intermediate 8) (1 g, 2.11 mmol) in DMF (10 mL) was treated at ambient temperature with potassium carbonate (0.583 g, 4.22 mmol) and methyl 3-(bromomethyl)benzoate (Alfa Aesar) (0.580 g, 2.53 mmol). The resulting mixture was stirred at 50° C. for 2 h and the LCMS then showed product as the major peak. The mixture was diluted with DCM (20 mL) and of water (20 mL). The organic phase was separated and the aqueous layer was further extracted with DCM (20 mL). The combined organic solutions were washed with brine (30 mL), dried over an hydrophobic frit, and concentrated under reduced pressure. The residue was loaded in dichloromethane to a silica 100 g cartridge and purified by chromatography on Flashmaster II using a 0-100% gradient B in A, A beeing neat DCM and B being a 5% EtOAC in DCM solution over 40 min. and then further purified on a second cartridge silica 70 g using a 0-100% gradient B in A, A beeing neat DCM and B being a 5% EtOAC in DCM solution over 40 min. The appropriate fractions were combined and evaporated in vacuo to give the title compound (571 mg, 44%) as a gum. LCMS (System A) RT=1.60 min, ES+ve m/z 639/641 (M+NH4)+.

後処理

  1. customThe organic phase was separated
  2. extractionthe aqueous layer was further extracted with DCM (20 mL)
  3. washThe combined organic solutions were washed with brine (30 mL)
  4. customdried over an hydrophobic frit
  5. concentrationconcentrated under reduced pressure
  6. custompurified by chromatography on Flashmaster II
  7. customover 40 min.
  8. customfurther purified on a second cartridge silica 70 g
  9. customover 40 min
  10. customevaporated in vacuo

出典と根拠

ORDレコード
ord-a6a36d4fb1c74a1f888b9fce71033356
出典データセット
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08304446B2

反応ノート

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