4-Methylmorpholine → HCID 72714674、化合物

HRID 57971

反応式

HRID 57971 の反応式
F[C:2]1[N:7]=[C:6]([N:8]2[C:16]3[CH:15]=[C:14]([C:17]4[CH:22]=[N:21][CH:20]=[C:19]([CH3:23])[N:18]=4)[N:13]=[CH:12][C:11]=3[CH:10]=[N:9]2)[CH:5]=[C:4]([CH:24]2[CH2:27][O:26][CH2:25]2)[CH:3]=1.[NH:28]1[CH2:33][CH2:32][CH2:31][C@H:30]([NH:34]C(=O)OC(C)(C)C)[CH2:29]1.CN1CCOCC1>CN1CCCC1=O>[CH3:23][C:19]1[N:18]=[C:17]([C:14]2[N:13]=[CH:12][C:11]3[CH:10]=[N:9][N:8]([C:6]4[N:7]=[C:2]([N:28]5[CH2:33][CH2:32][CH2:31][C@H:30]([NH2:34])[CH2:29]5)[CH:3]=[C:4]([CH:24]5[CH2:27][O:26][CH2:25]5)[CH:5]=4)[C:16]=3[CH:15]=2)[CH:22]=[N:21][CH:20]=1

参加物

5

反応物 3

HCID 79724-MethylmorpholineHCID 1514171tert-butyl N-[(3S)-piperidin-3-yl]carbamateHCID 867071531-[6-Fluoro-4-(oxetan-3-yl)-2-pyridyl]-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine

生成物 1

HCID 72714674HCID 72714674、化合物収率 27.4%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
100 °C

実験手順

A mixture of 1-[6-fluoro-4-(oxetan-3-yl)-2-pyridyl]-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine (0.1443 mmol; 63 mg), tert-butyl N-[(3S)-3-piperidyl]carbamate (0.4329 mmol, 80.7 mg), and N-Methylmorpholine (0.3607 mmol; 36.9 mg; 0.0401 mL) in 1-Methyl-2-pyrrolidinone (3 mL) in a sealed pressure vial was heated at 100° C. overnight. The mixture was cooled to room temperature. The solvents were removed. The residue was treated with 20% TFA in DCM at room temperature for 2 h. The mixture was concentrated and the residue was purified by reverse phase HPLC to afford 250 as an off-white solid (17.5 mg, 26%). 1H NMR (400 MHz, DMSO) δ 9.61-9.57 (s, 1H), 9.49-9.43 (s, 1H), 9.36-9.29 (s, 1H), 8.69-8.66 (s, 1H), 8.65-8.61 (s, 1H), 7.33-7.30 (s, 1H), 6.82-6.76 (s, 1H), 5.02-4.95 (m, 2H), 4.73-4.66 (t, J=6.3 Hz, 2H), 4.42-4.35 (d, J=13.2 Hz, 1H), 4.35-4.27 (dd, J=15.0, 7.2 Hz, 1H), 4.20-4.13 (d, J=10.7 Hz, 1H), 3.29-3.21 (m, 2H), 3.08-3.01 (m, 1H), 2.98-2.91 (s, 1H), 2.66-2.61 (s, 3H), 2.01-1.83 (m, 3H), 1.71-1.58 (d, J=13.4 Hz, 1H), 1.51-1.40 (d, J=10.8 Hz, 1H), 0.99-0.92 (t, J=7.3 Hz, 1H); MS (ESI) m/z: 443.2 [M+H]+

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. customThe solvents were removed
  3. additionThe residue was treated with 20% TFA in DCM at room temperature for 2 h
  4. concentrationThe mixture was concentrated
  5. customthe residue was purified by reverse phase HPLC

出典と根拠

ORDレコード
ord-2c331de0b1484cc499df59dd54230aaf
出典データセット
uspto-grants-2016_09
特許番号
US09434725B2

関連ノート

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