Carbon Dioxide → N-[(4R)-2-amino-2',2'-dimethyldispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetan]-6'-yl]-5-chloropyridine-2-carboxamide

HRID 873770Notes

Reaction equation

HRID 873770 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C:5]2([N:30]=1)[C:14]1([CH2:17][O:16][CH2:15]1)[C:13]([CH3:19])([CH3:18])[O:12][C:11]1[C:6]2=[CH:7][C:8]([NH:20][C:21]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][N:24]=2)=[O:22])=[CH:9][CH:10]=1.C(=O)=O>>[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([N:30]=1)[C:14]1([CH2:15][O:16][CH2:17]1)[C:13]([CH3:18])([CH3:19])[O:12][C:11]1[C:6]2=[CH:7][C:8]([NH:20][C:21]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][N:24]=2)=[O:22])=[CH:9][CH:10]=1

Participants

3

Reactant 2

HCID 280Carbon DioxideHCID 72548694N-(2-amino-2',2'-dimethyldispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetan]-6'-yl)-5-chloro pyridine-2-carboxamide

Product 1

HCID 72548947N-[(4R)-2-amino-2',2'-dimethyldispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetan]-6'-yl]-5-chloropyridine-2-carboxamideYield 44%

Procedure

N-(2-amino-2′,2′-dimethyldispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-6′-yl)-5-chloro pyridine-2-carboxamide (352 mg, 0.821 mmol) was subjected to chromatography using supercritical CO2 (supercritical CO2/[EtOH with 0.1% diethylamine]=60:40) on Chiralcel OD-H column (10×250 mm) eluting at a flow rate 10 mL/minute (40° C. column temperature). After concentration of collected fractions of the first peak (retention time=5.23 minutes) at reduced pressure, recrystallization of the residue with EtOH/water (1:1) provided a hydrate of N-[(4R)-2-amino-2′,2′-dimethyldispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-6′-yl]-5-chloropyridine-2-carboxamide (153 mg, 44%) as a crystal. After concentration of collected fractions of the second peak (retention time=8.16 minutes) at reduced pressure, recrystallization of the residue with EtOH/water (1:1) provided a hydrate of N-[(4S)-2-amino-2′,2′-dimethyldispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-6′-yl]-5-chloropyridine-2-carboxamide (152 mg) as a crystal.

Workup

  1. washeluting at a flow rate 10 mL/minute (40° C. column temperature)
  2. customAfter concentration of collected fractions of the first peak (retention time=5.23 minutes) at reduced pressure, recrystallization of the residue with EtOH/water (1:1)

Sources & evidence

ORD record
ord-808e86174df74bf09a4233719e0488e3
Source dataset
uspto-grants-2015_03
Patent number
US08975415B2

Reaction notes

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