Chloroacetyl chloride → HCID 86708552, Verbindung

HRID 921682Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921682
[Cl:1][CH2:2][C:3](Cl)=[O:4].[NH2:6][C@@H:7]1[CH2:12][CH2:11][N:10]([C:13]2[C:14]([Cl:46])=[C:15]([NH:21][C:22]3[N:27]=[C:26]([N:28]([CH:38]4[CH2:40][CH2:39]4)[CH2:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=4)[C:25]4=[N:41][CH:42]=[C:43]([C:44]#[N:45])[N:24]4[N:23]=3)[CH:16]=[C:17]([C:19]#[N:20])[CH:18]=2)[CH2:9][C@H:8]1[O:47][Si:48]([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49].C(N(CC)CC)C>ClCCl>[Si:48]([O:47][C@H:8]1[C@H:7]([NH:6][C:3](=[O:4])[CH2:2][Cl:1])[CH2:12][CH2:11][N:10]([C:13]2[CH:18]=[C:17]([C:19]#[N:20])[CH:16]=[C:15]([NH:21][C:22]3[N:27]=[C:26]([N:28]([CH:38]4[CH2:40][CH2:39]4)[CH2:29][C:30]4[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=4)[C:25]4=[N:41][CH:42]=[C:43]([C:44]#[N:45])[N:24]4[N:23]=3)[C:14]=2[Cl:46])[CH2:9]1)([C:51]([CH3:53])([CH3:54])[CH3:52])([CH3:49])[CH3:50]

Komponenten

5

Edukt 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 86708507(+/-)-2-((3-((3R,4R)-4-amino-3-((tert-butyldimethyl silyl)oxy) piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Produkt 1

HCID 86708552HCID 86708552, VerbindungAusbeute 99 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

2-chloroacetyl chloride (7.56 mg, 0.067 mmol) in dichloromethane (0.5 mL) was added to a mixture of (+/−)-2-((3-((3R,4R)-4-amino-3-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 171D), (39 mg, 0.056 mmol) and triethylamine (0.016 mL, 0.112 mmol) in dichloromethane (1 mL) at 0° C. and the reaction mixture was stirred at for 1 h. The reaction mixture was diluted with dichloromethane and washed with water. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (12 g column, eluting with 5-40% ethyl acetate/dichloromethane to afford (+/−)-N-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)-2-chloroacetamide (43 mg) as a white solid.

Aufarbeitung

  1. washwashed with water
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash chromatography on silica gel using an automated ISCO system (12 g column
  6. washeluting with 5-40% ethyl acetate/dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-803a69c37e4d462f8882f6fc46a5838d
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

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