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 594885Notes

Reaction equation

HRID 594885 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[O:9][CH2:10][C@@:11]2([C:21]3[C:16](=[CH:17][CH:18]=[C:19]([NH2:22])[CH:20]=3)[O:15][C:14]([CH3:24])([CH3:23])[C:13]32[CH2:26][CH2:25]3)[N:12]=1)([CH3:4])([CH3:3])[CH3:2].[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>[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[O:9][CH2:10][C@@:11]2([C:21]3[C:16](=[CH:17][CH:18]=[C:19]([NH:22][C:36]([C:33]4[CH:32]=[N:31][C:30]([CH:29]([F:39])[F:28])=[CH:35][N:34]=4)=[O:37])[CH:20]=3)[O:15][C:14]([CH3:24])([CH3:23])[C:13]32[CH2:25][CH2:26]3)[N:12]=1)([CH3:4])([CH3:2])[CH3:3]

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-73ceb0b166304a25a57110843feb88e5
Source dataset
uspto-grants-2016_01
Patent number
US09242973B2

Reaction notes

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