(R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-ol → HCID 89754455, compound

HRID 575284Notes

Reaction equation

HRID 575284 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH:10]([CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH2:9][N:8]3[CH:19]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[N:21]=[C:7]3[C:6]=2[CH:26]=1.[CH3:27][C:28]1[O:32][N:31]=[C:30]([C@:33]([OH:37])([C:35]#[CH:36])[CH3:34])[CH:29]=1>>[OH:37][C@:33]([C:30]1[CH:29]=[C:28]([CH3:27])[O:32][N:31]=1)([CH3:34])[C:35]#[C:36][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH:10]([CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH2:9][N:8]3[CH:19]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[N:21]=[C:7]3[C:6]=2[CH:26]=1

Participants

3

Reactant 2

HCID 58221468(R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-olHCID 89754468HCID 89754468, compound

Product 1

HCID 89754455HCID 89754455, compound

Procedure

Similar to as described in General Procedure G, racemic methyl 10-bromo-6-(morpholinomethyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate was reacted with (2R)-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol to produce methyl 10-((R)-3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-6-(morpholinomethyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate as a diasteromeric mixture. A suspension of methyl 10-((R)-3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-6-(morpholinomethyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate (220 mg, 0.45 mmol, 1.00 equiv) in aqueous ammonia (40 mL) was stirred overnight at 60° C. The resulting mixture was concentrated under vacuum and the residue was purified on a silica gel column with dichloromethane/methanol (20:1). This resulted in 43 mg (20%) of 10-((R)-3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-6-(morpholinomethyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide as a colorless solid. The two diasteromers were separated by Chiral-Prep-HPLC with the following conditions: Column, CHIRALPAK IC-3; mobile phase, Hex (0.1% TEA):EtOH=50/50; Detector, 254 nm. This resulted in 12.2 mg (30%) of Compound 1 and 15.3 mg (38%) Compound 2.

Sources & evidence

ORD record
ord-bb18c82144a243df8b9dae938849fe9d
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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