Ethanol → 4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-6-methoxy-N-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine

HRID 1842805ノート

反応式

HRID 1842805 の反応式
[CH3:1][N:2]([CH3:35])[C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[C:13]([N+:14]([O-])=O)=[CH:12][C:11]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[CH:25]=[N:26][N:27]5[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=45)[CH:21]=[CH:20][N:19]=3)=[C:10]([O:33][CH3:34])[CH:9]=2)[CH2:4]1.[NH4+].[Cl-].C(O)C>[Fe].O>[CH3:35][N:2]([CH3:1])[C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]([O:33][CH3:34])[C:11]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[CH:25]=[N:26][N:27]5[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=45)[CH:21]=[CH:20][N:19]=3)=[CH:12][C:13]=2[NH2:14])[CH2:4]1

参加物

6

反応物 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 71269755N-[4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2 回

生成物 1

HCID 866773094-[(3R)-3-dimethylaminopyrrolidin-1-yl]-6-methoxy-N-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine収率 82%

試薬・触媒・溶媒 2

HCID 23925Iron触媒HCID 962Water溶媒

実験手順

A mixture of N-[4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 154, 440 mg, 0.93 mmol), iron (311 mg, 5.56 mmol), NH4Cl (37.2 mg, 0.70 mmol), ethanol (15 mL) and water (5 mL) was heated at reflux for 1.5 h. After cooling the mixture was concentrated in vacuo. The resulting residue was triturated in 10% CH3OH in CH2Cl2 (20 mL) for 15 minutes and then filtered. The residues were triturated again with 10% CH3OH in CH2Cl2 (10 mL) and then filtered. The combined filtrates were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-10% methanolic ammonia in CH2Cl2 gave the title compound (339 mg, 82%) as a yellow solid after trituration with diethyl ether; 1H NMR: 1.73-1.83 (1H, m), 2.00-2.10 (1H, m), 2.20 (6H, s), 2.81-2.90 (1H, m), 2.92-3.00 (2H, m), 3.11-3.16 (1H, m), 3.17-3.24 (1H, m), 3.73 (3H, s), 4.28 (2H, br s), 6.71 (1H, s), 7.07 (1H, td), 7.20 (1H, d), 7.27 (1H, s), 7.37-7.42 (1H, m), 7.97 (1H, s), 8.30 (1H, d), 8.53 (1H, d), 8.76 (1H, s), 8.79 (1H, d); m/z: ES+ MH+ 445.33.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 1.5 h
  3. temperatureAfter cooling the mixture
  4. concentrationwas concentrated in vacuo
  5. customThe resulting residue was triturated in 10% CH3OH in CH2Cl2 (20 mL) for 15 minutes
  6. filtrationfiltered
  7. customThe residues were triturated again with 10% CH3OH in CH2Cl2 (10 mL)
  8. filtrationfiltered
  9. washThe combined filtrates were washed with brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customPurification by FCC
  13. washeluting with 0-10% methanolic ammonia in CH2Cl2

出典と根拠

ORDレコード
ord-31a2e15112a94b38a1f4ec0deee7327c
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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