반응식
Cl[C:2]1[N:10]=[C:9]([F:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:12]([CH3:14])[CH3:13].[CH3:15][N:16]1[CH:20]=[C:19]([NH2:21])[CH:18]=[N:17]1.CCN(C(C)C)C(C)C>C(O)CCC>[F:11][C:9]1[N:8]=[C:7]2[C:3]([N:4]=[CH:5][N:6]2[CH:12]([CH3:14])[CH3:13])=[C:2]([NH:21][C:19]2[CH:18]=[N:17][N:16]([CH3:15])[CH:20]=2)[N:10]=1참가 물질
실험 절차
To a solution of 6-chloro-2-fluoro-9-isopropyl-9H-purine (200 mg, 0.932 mmol), as prepared in step 1 of the alternate method of Example 2, in nBuOH, (4.66 mL) was added 1-methyl-1H-pyrazol-4-amine (109 mg, 1.12 mmol) and DIPEA (482 mg, 3.73 mmol) and the mixture stirred at ambient temperature for 6 hr to yield crude 2-fluoro-9-isopropyl-N-(1-methyl-1H-pyrazol-4-yl)-9H-purin-6-amine. (S)-3-(methylsulfonyl)-N-(pyrrolidin-3-yl)propanamide hydrochloride (289 mg, 1.12 mmol) was then added to the reaction mixture and heated at 100° C. for 16 hr. LCMS showed unreacted intermediate so the reaction was heated at 110° C. for another 24 hr. The reaction was then cooled to ambient temperature and potassium tert-butoxide (3.73 mL, 3.73 mmol) was added and the resulting mixture stirred at ambient temperature for 30 min. Water was added and the reaction was extracted with DCM (3×50 mL), then the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were dried with Na2SO4, concentrated, loaded onto silica and purified via flash chromatography using 0-20% EtOH/EtOAc to give the title compound (290 mg, 78% yield) as a pink solid, 1H NMR (400 MHz, DMSO-d6) δ ppm 9.56 (s, 1 H) 8.38 (d, J=6.72 Hz, 1 H) 7.97 (s, 1 H) 7.89 (s, 1 H) 7.75 (s, 1 H) 6.20-6.34 (m, 1 H) 6.05-6.18 (m, 1 H) 5.60 (dd, J=10.03, 2.32 Hz, 1 H) 4.56-4.73 (m, 1 H) 4.43 (br. s., 1 H) 3.76-3.92 (m, 4 H) 3.68 (d, J=5.14 Hz, 2 H) 3.43-3.51 (m, 1 H) 2.15-2.28 (m, 1 H) 1.87-1.99 (m, 1 H) 1.51 (d, J=6.85 Hz, 6 H). m/z for C19H25N9O 397.25 and 396.30 (M+H)+.
출처 및 근거
- ORD 기록
- ord-a431dab4814d48a6977fb0c89dae4fd5
- 출처 데이터셋
- uspto-grants-2016_03
- 특허 번호
- US09290496B2
연결된 노트
불러오는 중…