Diisopropylcarbodiimide → HCID 178495114, compound

HRID 2065808Notes

Reaction equation

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

Participants

Conditions

Temperature: 85 °C

Procedure

A KIMAX® tube is charged with 3-amino-6-[5-(2,4-difluorophenyl)-2-(3-methyloxetan-3-yl)-1H-imidazol-4-yl]pyridin-2-ol (2.28 g, 6.36 mmol) and ethanol (18 mL). (3S)-3-Isothiocyanato-1-methoxy-butane (1.39 g, 9.54 mmol) is added, the flask sealed, and the mixture is heated to 85° C. After 16 h, (3S)-3-isothiocyanato-1-methoxy-butane (700 mg) is added and the mixture is stirred for 48 h at 85° C. in the sealed tube. N,N′-diisopropylcarbodiimide (1.04 g) is added and the mixture is stirred 3 h at 85° C. in the sealed tube. The crude reaction mixture is concentrated under reduced pressure and the residue purified by normal phase chromatography (120 g silica-gel cartridge, hexane-ethanol). The desired compound elutes at 3% of ethanol to give the title compound as a brown solid (2.61 g, 87%). LC-ES/MS m/z 470 (M+1); [α]D22+42.2°, (c=0.50, methanol).

Workup

customthe flask sealed
stirringthe mixture is stirred 3 h at 85° C. in the sealed tube
customThe crude reaction mixture
concentrationis concentrated under reduced pressure
customthe residue purified by normal phase chromatography (120 g silica-gel cartridge, hexane-ethanol)

Sources & evidence

ORD record: ord-06231420416349fcb3e97d8269b4cd4a
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288548B2

Reaction notes

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