Diisopropylethylamine → HCID 178429372, 화합물

HRID 707366노트

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HRID 707366 반응식
FC(F)(F)S(O[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[N:8]=1)(=O)=O.Cl.[NH2:20][C@H:21]1[CH2:24][C@H:23]([N:25]2[C:29]3[N:30]=[CH:31][N:32]=[CH:33][C:28]=3[C:27]([CH3:35])([CH3:34])[C:26]2=[O:36])[CH2:22]1.C(N(CC)C(C)C)(C)C>CS(C)=O.O>[N:8]1[C:9]2[C:14](=[N:13][CH:12]=[CH:11][CH:10]=2)[CH:15]=[CH:16][C:7]=1[NH:20][C@H:21]1[CH2:24][C@H:23]([N:25]2[C:29]3[N:30]=[CH:31][N:32]=[CH:33][C:28]=3[C:27]([CH3:34])([CH3:35])[C:26]2=[O:36])[CH2:22]1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 866942231,5-Naphthyridin-2-yl trifluoromethanesulfonateHCID 178429370HCID 178429370, 화합물

생성물 1

HCID 178429372HCID 178429372, 화합물수율 71.6%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매

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온도
100 °C

실험 절차

To suspension of 1,5-naphthyridin-2(1H)-one (0.200 g, 1.368 mmol) in Pyridine (1 mL) was added slowly trifluoromethanesulfonic anhydride (0.050 mL, 0.298 mmol). After the addition, the reaction mixture was stirred at room temperature for 18 h. The solvent was evaporated under high vacuum and residue diluted with water and extracted with EtOAc. EtOAc was washed with water, brine, dried over Na2SO4 and concentrated to give crude 1,5-naphthyridin-2-yl trifluoromethanesulfonate. To this crude 1,5-naphthyridin-2-yl trifluoromethanesulfonate (100 mg) in DMSO (0.5 mL) was added 7-(trans-3-aminocyclobutyl)-5,5-dimethyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one hydrochloride, INTERMEDIATE 62, (0.05 g, 0.186 mmol) and N,N-diisopropylethylamine (0.032 mL, 0.186 mmol). The mixture was heated to 100° C. for 2 hours, diluted with water and extracted with EtOAc. EtOAc was concentrated and residue purified with ISCO using silical gel column eluting with 0-100% EtOAc/hexanes to give the title compound 7-(trans-3-((1,5-naphthyridin-2-yl)amino)cyclobutyl)-5,5-dimethyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (0.048 g, 0.133 mmol, 71.6% yield). m/z: 361.2; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.85 (s, 1 H) 8.62 (dd, J=4.21, 1.27 Hz, 1 H) 8.33 (s, 1 H) 8.07 (d, J=9.00 Hz, 1 H) 7.98 (d, J=8.22 Hz, 1 H) 7.45 (dd, J=8.51, 4.21 Hz, 1 H) 6.88 (d, J=9.00 Hz, 1 H) 5.46 (d, J=4.50 Hz, 1 H) 5.17-5.35 (m, 1 H) 4.79 (dd, J=7.92, 3.62 Hz, 1 H) 3.32-3.58 (m, 2 H) 2.44 (tt, J=10.03, 3.08 Hz, 2 H) 1.45 (s, 6 H).

후처리

  1. extractionextracted with EtOAc
  2. concentrationEtOAc was concentrated
  3. customresidue purified with ISCO
  4. washeluting with 0-100% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-85d3c7d0548142238e399fc87b332d74
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09174992B2

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