Water → N-(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-[(3S)-3-dimethylaminopyrrolidin-1-yl]-6-methoxybenzene-1,3-diamine

HRID 1842719

反応式

HRID 1842719 の反応式
[Cl:1][C:2]1[C:3]([C:28]2[CH:29]=[N:30][N:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=23)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([N+:15]([O-])=O)[C:12]([N:18]3[CH2:22][CH2:21][C@H:20]([N:23]([CH3:25])[CH3:24])[CH2:19]3)=[CH:11][C:10]=2[O:26][CH3:27])=[N:6][CH:7]=1.[NH4+].[Cl-].O>C(O)C.[Fe]>[Cl:1][C:2]1[C:3]([C:28]2[CH:29]=[N:30][N:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=23)=[N:4][C:5]([NH:8][C:9]2[C:10]([O:26][CH3:27])=[CH:11][C:12]([N:18]3[CH2:22][CH2:21][C@H:20]([N:23]([CH3:25])[CH3:24])[CH2:19]3)=[C:13]([NH2:15])[CH:14]=2)=[N:6][CH:7]=1

参加物

6

反応物 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 712702605-Chloro-N-{4-[(3S)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl}-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2 回

生成物 1

HCID 86677245N-(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-[(3S)-3-dimethylaminopyrrolidin-1-yl]-6-methoxybenzene-1,3-diamine収率 94%

試薬・触媒・溶媒 2

HCID 23925Iron触媒HCID 702Ethanol溶媒

実験手順

A mixture of 5-chloro-N-[4-[(3S)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 62, 295 mg, 0.58 mmol), iron (194 mg, 3.48 mmol) and NH4Cl (23 mg, 0.43 mmol) were heated at reflux in ethanol (12 mL) and water (4 mL) for 1.5 h. The mixture was then cooled and concentrated in vacuo. The residue was triturated in 10% CH3OH in CH2Cl2 (25 mL) for 15 minutes and then filtered. The residues were triturated again with 10% CH3OH in CH2Cl2 (25 mL) and 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 (260 mg, 94%) as a yellow gum; 1H NMR: 1.73-1.86 (1H, m), 2.01-2.12 (1H, m), 2.20 (6H, s), 2.81-2.91 (1H, m), 2.92-3.05 (2H, m), 3.16 (1H, dd), 3.2-3.27 (1H, m), 3.67 (3H, s), 4.25 (2H, d), 6.71 (1H, s), 6.93 (1H, s), 7.12 (1H, td), 7.3-7.37 (1H, m), 8.36 (1H, s), 8.38-8.46 (2H, m), 8.82 (1H, dt), 8.94 (1H, s); m/z: ES+ MH+ 479.5.

後処理

  1. temperaturewere heated
  2. temperatureThe mixture was then cooled
  3. concentrationconcentrated in vacuo
  4. customThe residue was triturated in 10% CH3OH in CH2Cl2 (25 mL) for 15 minutes
  5. filtrationfiltered
  6. customThe residues were triturated again with 10% CH3OH in CH2Cl2 (25 mL)
  7. filtrationfiltered
  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-33394ee73bea4469a191fbae5e9124af
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

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