Ethanol → 4-methoxy-6-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-N'-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine

HRID 1842814ノート

反応式

HRID 1842814 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[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=23)[CH:25]=[CH:24][N:23]=1.[NH4+].[Cl-].C(O)C>[Fe].O>[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[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=23)[CH:25]=[CH:24][N:23]=1

参加物

6

反応物 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 71240856N-[2-methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2 回

生成物 1

HCID 866773174-methoxy-6-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-N'-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine収率 89.2%

試薬・触媒・溶媒 2

HCID 23925Iron触媒HCID 962Water溶媒

実験手順

A mixture of N-[2-methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 163, 404 mg, 0.83 mmol), iron (278 mg, 4.98 mmol), NH4Cl (33.3 mg, 0.62 mmol), ethanol (15 mL) and water (5 mL) was heated at reflux for 1.5 h. After cooling, the mixture was filtered and the residues were washed with 1:10 CH3OH—CH2Cl2 (20 mL). The combined filtrates were concentrated in vacuo onto silica. Purification by FCC, eluting with 1-10% methanolic ammonia in CH2Cl2 gave the title compound (338 mg, 89%) as a yellow solid; 1H NMR: 1.72 (2H, dt), 2.11 (2H, dd), 2.42 (3H, s), 2.66 (2H, t), 3.63 (2H, d), 3.72 (3H, s), 3.87 (2H, d), 4.03 (2H, s), 6.29 (1H, s), 7.06 (1H, td), 7.10 (1H, s), 7.16 (1H, d), 7.35-7.42 (1H, m), 7.93 (1H, s), 8.27 (1H, d), 8.52 (1H, d), 8.74 (1H, s), 8.77 (1H, t); m/z: ES+ MH+ 457.36.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 1.5 h
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered
  5. washthe residues were washed with 1:10 CH3OH—CH2Cl2 (20 mL)
  6. concentrationThe combined filtrates were concentrated in vacuo onto silica
  7. customPurification by FCC
  8. washeluting with 1-10% methanolic ammonia in CH2Cl2

出典と根拠

ORDレコード
ord-12a09bd2840d4612a52ad5415604e021
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

反応ノート

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