Water → ethyl 4-(5-chloropyrazin-2-yl)-2-[(3R,4S)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-1,3-thiazole-5-carboxylate

HRID 655734Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 655734
Br[C:2]1[S:3][C:4]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:5]([C:7]2[CH:12]=[N:11][C:10]([Cl:13])=[CH:9][N:8]=2)[N:6]=1.[Cl:19][C:20]1[C:24]([Cl:25])=[C:23]([CH3:26])[NH:22][C:21]=1[C:27]([NH:29][C@H:30]1[CH2:35][CH2:34][NH:33][CH2:32][C@H:31]1[O:36][CH3:37])=[O:28].C(N(CC)C(C)C)(C)C.O>CN1CCCC1=O>[Cl:13][C:10]1[N:11]=[CH:12][C:7]([C:5]2[N:6]=[C:2]([N:33]3[CH2:34][CH2:35][C@H:30]([NH:29][C:27]([C:21]4[NH:22][C:23]([CH3:26])=[C:24]([Cl:25])[C:20]=4[Cl:19])=[O:28])[C@H:31]([O:36][CH3:37])[CH2:32]3)[S:3][C:4]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[N:8][CH:9]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 58074997Ethyl 2-bromo-4-(5-chloropyrazin-2-yl)-1,3-thiazole-5-carboxylate2×HCID 667076203,4-dichloro-N-[(3R,4S)-3-methoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide

Produkt 1

HCID 59402528ethyl 4-(5-chloropyrazin-2-yl)-2-[(3R,4S)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-1,3-thiazole-5-carboxylateAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
52.5 °C

Versuchsvorschrift

Ethyl 2-bromo-4-(5-chloropyrazin-2-yl)-1,3-thiazole-5-carboxylate (Intermediate 47, 120 mg, 0.3960 mM) was added to a solution of 3,4-dichloro-N-[(3R,4S)-3-methoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide (WO2006087543, 127 mg, 0.4158 mM) and N,N-diisopropylethylamine (159.6 mg, 1.247 mM) in N-methyl 2-pyrrolidinone (1.0 mL) and the resulting reaction mixture was stirred at 50-55° C. for 1 h. The reaction mixture was cooled to room temperature and then poured into water (40 mL). The resulting solid was collected by filtration and dried to afford ethyl 4-(5-chloropyrazin-2-yl)-2-[(3R,4S)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-1,3-thiazole-5-carboxylate 140 mg (90%) of as an off-white solid.

Aufarbeitung

  1. customthe resulting reaction mixture
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationThe resulting solid was collected by filtration
  4. customdried

Quellen und Nachweise

ORD-Eintrag
ord-53a6dbf357ba40f2a7f91196c8ecc43e
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071605B2

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