1-Hydroxybenzotriazole → tert-butyl [(4'R)-6'-({[5-(difluoromethyl)pyrazin-2-yl]carbonyl}amino)-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-yl]carbamate

HRID 873738Notes

Reaction equation

HRID 873738 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C@@:13]3([CH2:17][O:16][C:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[N:14]3)[C:10]3([CH2:12][CH2:11]3)[C:9]([CH3:27])([CH3:26])[O:8][C:5]2=[CH:6][CH:7]=1.[F:28][CH:29]([F:39])[C:30]1[N:31]=[CH:32][C:33]([C:36](O)=[O:37])=[N:34][CH:35]=1.N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>C(Cl)(Cl)Cl>[F:39][CH:29]([F:28])[C:30]1[N:31]=[CH:32][C:33]([C:36]([NH:1][C:2]2[CH:3]=[C:4]3[C@@:13]4([CH2:17][O:16][C:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[N:14]4)[C:10]4([CH2:11][CH2:12]4)[C:9]([CH3:27])([CH3:26])[O:8][C:5]3=[CH:6][CH:7]=2)=[O:37])=[N:34][CH:35]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 574685755-Difluoromethympyrazine-2-carboxylic acidHCID 86724280tert-butyl [(4'R)-6'-amino-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-yl]carbamate

Product 1

HCID 86724286tert-butyl [(4'R)-6'-({[5-(difluoromethyl)pyrazin-2-yl]carbonyl}amino)-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-yl]carbamateYield 61.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To an ice-water cooled mixture of tert-butyl [(4′R)-6′-amino-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-yl]carbamate (430 mg, 1.15 mmol), 5-(difluoromethyl)pyrazine-2-carboxylic acid (221 mg, 1.27 mmol) and 1H-benzotriazol-1-ol (170 mg, 1.26 mmol) in chloroform (8.6 ml) was added N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (244 mg, 1.28 mmol). The mixture was stirred at room temperature overnight and directly purified by silica gel column chromatography (precolumn: basic silica gel, main column: neutral silica gel, hexane/ethyl acetate=2:1-1:1-0:100) to afford tert-butyl [(4′R)-6′-({[5-(difluoromethyl)pyrazin-2-yl]carbonyl}amino)-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-yl]carbamate (373 mg).

Workup

  1. customdirectly purified by silica gel column chromatography (precolumn: basic silica gel, main column: neutral silica gel, hexane/ethyl acetate=2:1-1:1-0:100)

Sources & evidence

ORD record
ord-e709b5ddb8094fe4927520895fae2c37
Source dataset
uspto-grants-2015_03
Patent number
US08975415B2

Reaction notes

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