9-Bromo-4,4-difluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester → (R)-methyl 4,4-difluoro-9-((3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylate

HRID 575354Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 575354
Br[C:2]1[CH:21]=[CH:20][C:5]2[O:6][CH2:7][C:8]([F:19])([F:18])[C:9]3[S:13][C:12]([C:14]([O:16][CH3:17])=[O:15])=[N:11][C:10]=3[C:4]=2[CH:3]=1.[C:22]([C@:24]1([OH:31])[CH2:28][CH2:27][N:26]([CH3:29])[C:25]1=[O:30])#[CH:23]>>[F:18][C:8]1([F:19])[C:9]2[S:13][C:12]([C:14]([O:16][CH3:17])=[O:15])=[N:11][C:10]=2[C:4]2[CH:3]=[C:2]([C:23]#[C:22][C@:24]3([OH:31])[CH2:28][CH2:27][N:26]([CH3:29])[C:25]3=[O:30])[CH:21]=[CH:20][C:5]=2[O:6][CH2:7]1

Komponenten

3

Edukt 2

HCID 866931449-Bromo-4,4-difluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl esterHCID 86693296(R)-3-ethynyl-3-hydroxy-1-methylpyrrolidin-2-one

Produkt 1

HCID 86693393(R)-methyl 4,4-difluoro-9-((3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylate

Versuchsvorschrift

Methyl 9-bromo-4,4-difluoro-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylate was reacted with (3R)-3-ethynyl-3-hydroxy-1-methyl-pyrrolidin-2-one similarly to as described in General Procedure F with non-critical modifications to afford crude (R)-methyl 4,4-difluoro-9-((3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylate. Crude (R)-methyl 4,4-difluoro-9-((3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylate was subjected to General Procedure M to afford 21.2 mg (38%) of 4,4-difluoro-9-[2-[(3R)-3-hydroxy-1-methyl-2-oxo-pyrrolidin-3-yl]ethynyl]-5H-[1]benzoxepino[5,4-d]thiazole-2-carboxamide. M+1=420; 1H NMR (400 MHz, DMSO-d6) δ 8.73 (s, 1H), 8.63 (d, J=2.2 Hz, 1H), 8.15 (s, 1H), 7.49 (dd, J=8.4, 2.2 Hz, 1H), 7.24 (d, J=8.4 Hz, 1H), 6.43 (s, 1H), 4.76 (t, J=10.6 Hz, 2H), 3.43-3.29 (m, 2H), 2.81 (s, 2H), 2.46 (ddd, J=12.8, 6.4, 5.1 Hz, 1H), 2.26-2.15 (m, 1H).

Quellen und Nachweise

ORD-Eintrag
ord-77c867d992a94952ae944dd2974b7144
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09034866B2

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