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

HRID 575366Notes

Reaction equation

HRID 575366 reaction equation
Br[C:2]1[CH:21]=[CH:20][C:5]2[O:6][CH2:7][C:8]([OH:19])([CH3:18])[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]>>[OH:19][C:8]1([CH3:18])[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

Participants

3

Reactant 2

HCID 866931469-Bromo-4-hydroxy-4-methyl-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

Product 1

HCID 86693409methyl 4-hydroxy-9-(((R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)-4-methyl-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylate

Procedure

Methyl 9-bromo-4-hydroxy-4-methyl-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylate (0.11 g) 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 methyl 4-hydroxy-9-(((R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)-4-methyl-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylate which was directly subjected to conditions described in General Procedure M to afford 5 mg and 5.6 mg (9% overall yield) after reverse phase purification then chiral separation. The absolute stereochemistry at the 4-hydroxyl substitution position for each isomer was not determined. M+1=414.0.

Sources & evidence

ORD record
ord-feeb3eceed234f8d98ac1ec22555ceda
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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