Diisopropylcarbodiimide → HCID 178467898, compound

HRID 2065794Notes

Reaction equation

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

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of methyl 1-[4-(5-amino-6-hydroxy-2-pyridyl)-5-(2,4-difluorophenyl)-1H-imidazol-2-yl]cyclopropanecarboxylate (4 g, 10.35 mmol) and (2S)-1-ethoxy-2-isothiocyanato-propane (2.379 g, 15.53 mmol) are dissolved in ethanol (34 mL). The mixture is heated to 85° C. in a sealed flask for 16 h. Diisopropyl carbodiimide (3.21 g, 20.71 mmol) is added dropwise and the mixture is stirred at 85° C. for 16 h, after which time an additional 3 g of diisopropyl carbodiimide is added and the mixture is heated at 85° C. for an additional 4 h. The solvent is evaporated and the residue is purified by normal phase chromatography (120 g silica-gel cartridge, using a hexane-ethanol gradient to afford the title compound (1.180 g, 24%). LC-ES/MS m/z 498.1 (M+1).

Workup

temperaturethe mixture is heated at 85° C. for an additional 4 h
customThe solvent is evaporated
customthe residue is purified by normal phase chromatography (120 g silica-gel cartridge

Sources & evidence

ORD record: ord-df2ea40193c34054beb496ad62209de3
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288548B2

Reaction notes

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