Diisopropylethylamine → HCID 178429372、化合物

HRID 707366ノート

反応式

HRID 707366 の反応式
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

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 866942231,5-Naphthyridin-2-yl trifluoromethanesulfonateHCID 178429370HCID 178429370、化合物

生成物 1

HCID 178429372HCID 178429372、化合物収率 71.6%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-85d3c7d0548142238e399fc87b332d74
出典データセット
uspto-grants-2015_11
特許番号
US09174992B2

反応ノート

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