Water → 4-methoxy-6-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-N'-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842794ノート

反応式

HRID 1842794 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:12][C:11]3([N:16]([CH3:17])[CH2:15][CH2:14][CH2:13]3)[CH2:10]2)[C:6]([N+:18]([O-])=O)=[CH:5][C:4]=1[NH:21][C:22]1[N:27]=[C:26]([C:28]2[CH:29]=[N:30][N:31]3[CH2:36][CH2:35][CH2:34][CH2:33][C:32]=23)[CH:25]=[CH:24][N:23]=1.[NH4+].[Cl-].O>C(O)C.[Fe]>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:10][C:11]3([N:16]([CH3:17])[CH2:15][CH2:14][CH2:13]3)[CH2:12]2)[C:6]([NH2:18])=[CH:5][C:4]=1[NH:21][C:22]1[N:27]=[C:26]([C:28]2[CH:29]=[N:30][N:31]3[CH2:36][CH2:35][CH2:34][CH2:33][C:32]=23)[CH:25]=[CH:24][N:23]=1

参加物

6

反応物 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 71240861N-[2-Methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine2 回

生成物 1

HCID 866772994-methoxy-6-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-N'-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine収率 84%

試薬・触媒・溶媒 2

HCID 23925Iron触媒HCID 702Ethanol溶媒

実験手順

N-[2-Methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 142, 320 mg, 0.65 mmol), iron (219 mg, 3.91 mmol) and NH4Cl (26.2 mg, 0.49 mmol) were heated at reflux in ethanol (18 mL) and water (6 mL) for 4 h. The mixture was then cooled, filtered and concentrated in vacuo. The resulting residue was triturated in 10% CH3OH in CH2Cl2 (15 mL) for 15 minutes and the mixture was then filtered. The residues were re-triturated with 10% CH3OH in CH2Cl2 (15 mL) and the mixture was then filtered. The combined filtrates were washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by FCC, eluting with 2% 7N methanolic ammonia in CH2Cl2 gave the title compound (251 mg, 84%) as a brown gum which crystallised on standing; 1H NMR: 1.64-1.76 (2H, m), 1.75-1.87 (2H, m), 1.91-2.03 (2H, m), 2.08 (2H, dd), 2.39 (3H, s), 2.63 (2H, t), 3.06 (2H, t), 3.56 (2H, d), 3.72 (3H, s), 3.82 (2H, d), 4.01 (2H, s), 4.10 (2H, t), 6.25 (1H, s), 6.91 (1H, d), 7.21 (1H, s), 7.67 (1H, s), 8.04 (1H, s), 8.23 (1H, d); m/z: ES+ MH+ 461.37.

後処理

  1. temperatureThe mixture was then cooled
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was triturated in 10% CH3OH in CH2Cl2 (15 mL) for 15 minutes
  5. filtrationthe mixture was then filtered
  6. customThe residues were re-triturated with 10% CH3OH in CH2Cl2 (15 mL)
  7. filtrationthe mixture was then filtered
  8. washThe combined filtrates were washed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customPurification by FCC
  12. washeluting with 2% 7N methanolic ammonia in CH2Cl2

出典と根拠

ORDレコード
ord-8bf300b27992425e8bd5a0f8a735d0c9
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

反応ノート

読み込み中…