Potassium Carbonate → 5-amino-N-(5-(4-aminoazepan-1-yl)-1-ethyl-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)thiazole-4-carboxamide

온도

60 °C

A solution of tert-butyl 2-(2,6-difluorophenyl)-4-(1-ethyl-5-(4-(2,2,2-trifluoroacetamido)azepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate (0.17 g, 0.26 mmol) in HCl in 1,4-dioxane (4 M, 5 mL) was allowed to stand at room temperature for 40 hr. The reaction mixture was concentrated under reduced pressure and the residue dissolved in 50% aqueous MeOH (20 mL). K2CO3 (1.22 g, 8.84 mmol) was added and the mixture heated at 60° C. for 3 hr. The mixture was allowed to cool, concentrated to approximately 5 mL and extracted with DCM. The combined organic layers were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue by passing through an SCX column washing with DCM and MeOH and eluting with 1 N ammonia in MeOH gave 241 as a cream solid (118 mg, 99%). 1H-NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 7.92 (s, 1H), 7.36-7.28 (m, 1H), 7.06-6.97 (m, 2H), 6.14 (s, 2H), 4.05 (q, J=7 Hz, 2H), 3.29-3.12 (m, 5H), 2.02-1.88 (m, 3H), 1.75-1.60 (m, 3H), 1.43 (t, J=7 Hz, 3H). RNH2 not seen. LCMS (ES+) m/z 462.0 (M+1).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionthe residue dissolved in 50% aqueous MeOH (20 mL)
3. temperatureto cool
4. concentrationconcentrated to approximately 5 mL
5. extractionextracted with DCM
6. customThe combined organic layers were passed through a phase separation cartridge
7. customthe solvent removed under reduced pressure
8. customPurification of the residue
9. washwashing with DCM and MeOH
10. washeluting with 1 N ammonia in MeOH

ORD 기록

ord-9dc734020ef74d459680ba107c3729b0

출처 데이터셋

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08669361B2