Trifluoroacetic acid → 1-[2-(4-Fluoro-3-trifluoromethyl-benzylamino)-ethyl]-3-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-urea

HRID 550831

Reaction equation

FC(F)(F)C(O)=O.[CH3:8][O:9][C:10]1[C:11]2[N:18]=[C:17]([NH:19][C:20]([N:22]3CC[CH:24]([NH2:27])[CH2:23]3)=[O:21])[S:16][C:12]=2[N:13]=[CH:14][N:15]=1.[F:28][C:29]1[CH:36]=[CH:35][C:32]([CH:33]=O)=[CH:31][C:30]=1[C:37]([F:40])([F:39])[F:38].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C>CO>[F:28][C:29]1[CH:36]=[CH:35][C:32]([CH2:33][NH:27][CH2:24][CH2:23][NH:22][C:20]([NH:19][C:17]2[S:16][C:12]3[N:13]=[CH:14][N:15]=[C:10]([O:9][CH3:8])[C:11]=3[N:18]=2)=[O:21])=[CH:31][C:30]=1[C:37]([F:38])([F:39])[F:40]

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of the trifluoroacetic acid salt of 3-amino-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (176 mg, 0.46 mmol) in methanol (6 ml), 4-fluoro-3-(trifluoromethyl) benzaldehyde (90 mg, 0.46 mmol) and sodium triacetoxyborohydride (293 mg, 1.38 mmol) at 25° C. The resulting solution was stirred at 25° C. overnight. At this time, the reaction mixture was treated with triethylamine (200 mL, 1.44 mmol) and then was stirred for an additional 24 h. At this time, the reaction was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, gradient elution 95/5 methylene chloride/methanol) afforded 1-[2-(4-fluoro-3-trifluoromethyl-benzylamino)-ethyl]-3-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-urea (37 mg, 18%); ES-HRMS m/e calcd for C17H16F4N6O2S (M+H)+ 445.1065, found 445.1065.

Workup

customat 25° C
stirringwas stirred for an additional 24 h
concentrationAt this time, the reaction was concentrated in vacuo
washFlash chromatography (Merck Silica gel 60, 230-400 mesh, gradient elution 95/5 methylene chloride/methanol)

Sources & evidence

ORD record: ord-ba39de26c4c24720851a8cbd412f5c07
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07947692B2

Linked notes

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