HOAt → Ethyl 4-(2-bromo-4-fluorophenyl)-6-(((S)-3-(methoxycarbamoyl)morpholino)methyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate

HRID 524626Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[N:14]=[C:13]([C:15]2[S:16][CH:17]=[CH:18][N:19]=2)[NH:12][C:11]([CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH:22]2[C:27](O)=[O:28])=[C:10]1[C:30]([O:32][CH2:33][CH3:34])=[O:31].Cl.[CH3:36][O:37][NH2:38].CCN=C=NCCCN(C)C.Cl.C1C=NC2N(O)N=NC=2C=1>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:10]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:11]([CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][C@H:22]2[C:27](=[O:28])[NH:38][O:37][CH3:36])[NH:12][C:13]([C:15]2[S:16][CH:17]=[CH:18][N:19]=2)=[N:14]1

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of (3S)-4-(((6-(2-bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholine-3-carboxylic acid (0.5 g, 0.9 mmol), O-methylhydroxylamine hydrochloride (0.2 g, 2.25 mmol), EDC.HCl (1 g, 5.2 mmol), HOAt (1 g, 7.3 mmol) and TEA (1.45 g, 14.3 mmol) in DCM (30 mL) was stirred at 0 t for 1 hour. Then the mixture was warmed to 25° C. and stirred for another 10 hours. The mixture was concentrated in vacuo and the residue was purified by a silica gel column chromatography (DCM/MeOH (V/V)=30/1) to give the title compound as a yellow solid (0.4 g, 76%). The compound was characterized by the following spectroscopic data:

Workup

stirringstirred for another 10 hours
concentrationThe mixture was concentrated in vacuo
customthe residue was purified by a silica gel column chromatography (DCM/MeOH (V/V)=30/1)

Sources & evidence

ORD record: ord-008bcd48ed7841c69fa4a027522ac7f1
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340538B2

Reaction notes

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