Trifluoroacetic acid → (RS)-1-(2-cyano-4-morpholin-2-yl-phenyl)-3-(3-cyano-phenyl)-urea

HRID 571829Notes

Reaction equation

FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][O:18][CH:17]([C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[CH:32]=3)=[O:29])=[C:23]([C:39]#[N:40])[CH:22]=2)[CH2:16]1)=O)(C)(C)C.[OH-].[Na+]>O.C(#N)C>[C:39]([C:23]1[CH:22]=[C:21]([CH:17]2[O:18][CH2:19][CH2:20][NH:15][CH2:16]2)[CH:26]=[CH:25][C:24]=1[NH:27][C:28]([NH:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[CH:32]=1)=[O:29])#[N:40]

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of trifluoroacetic acid (22 μl) in water (3 ml) was added a solution of (RS)-2-{3-cyano-4-[3-(3-cyano-phenyl)-ureido]-phenyl}-morpholine-4-carboxylic acid tert-butyl ester (13 mg) in acetonitrile (1.5 ml). The reaction mixture was then capped and the mixture was shaken at 80° C. for 4 h. The reaction mixture was then cooled to room temperature and poured into 1 M aq. NaOH and the resulting mixture was extracted twice with EtOAc. The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash column chromatography (Isolute® Flash-NH2 from Separtis); gradient: heptane/EtOAc/MeOH) to afford (RS)-1-(2-cyano-4-morpholin-2-yl-phenyl)-3-(3-cyano-phenyl)-urea (6 mg, 52%) as a light brown solid. MS (ISP): 348.1 ([M+H]+).

Workup

customThe reaction mixture was then capped
temperatureThe reaction mixture was then cooled to room temperature
extractionthe resulting mixture was extracted twice with EtOAc
dry with materialThe organic layers were dried over Na2SO4
concentrationconcentrated in vacuo
customThe crude material was purified by flash column chromatography (Isolute® Flash-NH2 from Separtis)

Sources & evidence

ORD record: ord-cc8856ee99554275a0186d659cf7ffd0
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029370B2

Reaction notes

Loading…