2-(Pyridin-2-yl)but-3-yn-2-ol → 4-(Dimethylamino)-8-fluoro-9-(3-hydroxy-3-(pyridin-2-yl)but-1-yn-1-yl)-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxamide

HRID 575247Notes

Reaction equation

HRID 575247 reaction equation
Br[C:2]1[C:21]([F:22])=[CH:20][C:5]2[O:6][CH2:7][CH:8]([N:17]([CH3:19])[CH3:18])[C:9]3[S:13][C:12]([C:14]([NH2:16])=[O:15])=[N:11][C:10]=3[C:4]=2[CH:3]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]([OH:33])([C:31]#[CH:32])[CH3:30]>>[CH3:18][N:17]([CH3:19])[CH:8]1[C:9]2[S:13][C:12]([C:14]([NH2:16])=[O:15])=[N:11][C:10]=2[C:4]2[CH:3]=[C:2]([C:32]#[C:31][C:29]([OH:33])([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=3)[CH3:30])[C:21]([F:22])=[CH:20][C:5]=2[O:6][CH2:7]1

Participants

3

Reactant 2

HCID 167625022-(Pyridin-2-yl)but-3-yn-2-olHCID 89754597Racemic 9-bromo-4-(dimethylamino)-8-fluoro-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxamide

Product 1

HCID 897549204-(Dimethylamino)-8-fluoro-9-(3-hydroxy-3-(pyridin-2-yl)but-1-yn-1-yl)-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxamide

Procedure

Similar to as described in General Procedure G, racemic 9-bromo-4-(dimethylamino)-8-fluoro-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxamide was reacted with racemic 2-(pyridin-2-yl)but-3-yn-2-ol to give an isomeric mixture of the titled compound. The mixture (80 mg) was separated by Chiral-Prep-HPLC with the following conditions (2#-Gilson Gx 281(HPLC-09)): Column, CHIRALPAK AD-H SFC, 5*25 cm, 5 um; mobile phase, Hex (0.2% TEA) and ethanol (0.2% TEA) (hold 30.0% ethanol (0.2% TEA) in 30 min); Detector, UV 220/254 nm to give 1st 3.7 mg (2%) of Compound 1, then 10.2 mg (4%) of Compounds 2 and 18.6 mg (8%) Compound 3. The stereochemistry of these compounds has not been assigned.

Workup

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Sources & evidence

ORD record
ord-da8a0dbbff3744f4994fd30687e8f057
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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