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N-methyl-2-pyrrolidone → tert-butyl (3R)-3-{[5-carbamoyl-6-({-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-3-(prop-1-en-2-yl)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate

HRID 1526191
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1526191
[C:1]([C:4]1[N:5]=[C:6]([C:24](O)([CH3:26])[CH3:25])[C:7]([O:11][C@@H:12]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]2)=[N:8][C:9]=1Cl)(=[O:3])[NH2:2].[CH3:28][N:29]1[CH2:34][CH2:33][N:32]([CH:35]2[CH2:40][CH2:39][N:38]([C:41]3[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=3)[CH2:37][CH2:36]2)[CH2:31][CH2:30]1.C(N(C(C)C)CC)(C)C.CN1CCCC1=O>O>[C:1]([C:4]1[N:5]=[C:6]([C:24]([CH3:26])=[CH2:25])[C:7]([O:11][C@@H:12]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]2)=[N:8][C:9]=1[NH:45][C:44]1[CH:46]=[CH:47][C:41]([N:38]2[CH2:39][CH2:40][CH:35]([N:32]3[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]3)[CH2:36][CH2:37]2)=[CH:42][CH:43]=1)(=[O:3])[NH2:2]
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Komponenten

6

Edukt 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 580157484-(4-(4-Methyl-1-piperazinyl)-1-piperidinyl)benzenamineHCID 117675582tert-butyl (3R)-3-{[5-carbamoyl-6-chloro-3-(2-hydroxypropan-2-yl)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate

Produkt 1

HCID 117675492
tert-butyl (3R)-3-{[5-carbamoyl-6-({-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-3-(prop-1-en-2-yl)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate
Ausbeute 65,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of tert-butyl (3R)-3-{[5-carbamoyl-6-chloro-3-(2-hydroxypropan-2-yl)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate (300 mg), 4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]aniline (680 mg), diisopropylethylamine (400 μL), and N-methylpyrrolidone (1.2 mL) was reacted in a microwave reaction device at 180° C. for 1 hour. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1), and then washed with diisopropyl ether to obtain tert-butyl (3R)-3-{[5-carbamoyl-6-({-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-3-(prop-1-en-2-yl)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate (304 mg) as a yellow solid.

Aufarbeitung

  1. customwas reacted in a microwave reaction device at 180° C. for 1 hour
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1)
  6. washwashed with diisopropyl ether

Quellen und Nachweise

ORD-Eintrag
ord-c2fa998181cb46b987ee422d602faa4c
Quelldatensatz
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09085540B2

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