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

HRID 594884Notes

Reaction equation

HRID 594884 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].[CH3:28][O:29][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>ClCCl>[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]([O:29][CH3:28])=[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 457898115-Methoxy-2-pyrazinecarboxylic 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 86724285tert-butyl [(4'R)-6'-{[(5-methoxypyrazin-2-yl)carbonyl]amino}-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-yl]carbamateYield 79.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of tert-butyl[(4′R)-6′-amino-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-yl]carbamate (100 mg, 0.268 mmol), 5-methoxypyrazine-2-carboxylic acid (45 mg, 0.30 mmol) and 1H-benzotriazol-1-ol (40 mg, 0.29 mmol) in dichloromethane (2 mL) was added N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (57 mg, 0.30 mmol). The mixture was stirred at room temperature for 3 hours and directly purified by silica gel column chromatography (precolumn: NH-silica gel, main column: neutral silica gel, hexane/ethyl acetate=2:1-1:1-0:1) to afford tert-butyl[(4′R)-6′-{[(5-methoxypyrazin-2-yl)carbonyl]amino}-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-yl]carbamate (108 mg).

Workup

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

Sources & evidence

ORD record
ord-dcf3f75d533a4a5fa1e7f3289d4f49eb
Source dataset
uspto-grants-2016_01
Patent number
US09242973B2

Reaction notes

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