Trifluoroacetic acid → Trifluoroacetic acid

Reaktionsgleichung

C([O:8][C:9]1[N:14]=[C:13]2[S:15][C:16]([NH:18][C:19]3[O:20][C@:21]4([CH2:29][N:30]=3)[CH:26]3[CH2:27][CH2:28][N:23]([CH2:24][CH2:25]3)[CH2:22]4)=[N:17][C:12]2=[CH:11][CH:10]=1)C1C=CC=CC=1.[C:31]([OH:37])([C:33]([F:36])([F:35])[F:34])=[O:32]>>[N:23]12[CH2:24][CH2:25][CH:26]([CH2:27][CH2:28]1)[C@@:21]1([O:20][C:19]([NH:18][C:16]3[S:15][C:13]4[NH:14][C:9](=[O:8])[CH:10]=[CH:11][C:12]=4[N:17]=3)=[N:30][CH2:29]1)[CH2:22]2.[C:31]([OH:37])([C:33]([F:36])([F:35])[F:34])=[O:32]

Komponenten

Edukt 2

HCID 6422Trifluoroacetic acid

HCID 58088124(R)-N-(5-(benzyloxy)thiazolo[5,4-b]pyridin-2-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine

Produkt 2

HCID 6422Trifluoroacetic acidAusbeute 39,8 %

HCID 58088071(R)-2-(4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octane]-2-ylamino)thiazolo[5,4-b]pyridin-5(4H)-one

Versuchsvorschrift

(R)—N-(5-(benzyloxy)thiazolo[5,4-b]pyridin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (390 mg, 0.925 mmol) was dissolved in TFA and allowed to react for 4 hours at ambient temperature, at which time LCMS and TLC showed the starting material to be mostly consumed. The TFA was removed in vacuo and the crude mixture was purified by preparative HPLC. The combined product fractions were concentrated in vacuo and triturated with ether to afford (R)-2-(4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octane]-2-ylamino)thiazolo[5,4-b]pyridin-5(4H)-one, TFA (164 mg, 0.368 mmol, 39.8% yield). M.P. 245 (dec). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.99 (br. s., 1 H) 9.05 (br. s., 1 H) 7.81 (d, J=8.53 Hz, 1 H) 6.65 (d, J=8.78 Hz, 1 H) 3.96 (d, J=10.29 Hz, 1 H) 3.82 (d, J=Hz, 1 H) 3.63-3.78 (m, 2 H) 3.36-3.47 (m, 1 H) 3.16-3.34 (m, 3 H) 2.43 (br. s., 1 H) 2.16 (br. s., 1 H) 1.76-2.07 (m, 3 H). MS (LC/MS) R.T.=0.50; [M+H]+=332.15.