Hydrochloric Acid → 1-{1-[3-(4-Fluorophenyl)-2,2-dimethylpropyl]-piperidin-3-ylmethyl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea

HRID 896521ノート

反応式

HRID 896521 の反応式
B.O1CCCC1.[F:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15]([CH3:42])([CH3:41])[C:16]([N:18]2[CH2:23][CH2:22][CH2:21][CH:20]([CH2:24][NH:25][C:26]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]4[N:39]([CH3:40])[N:38]=[N:37][N:36]=4)[CH:30]=3)=[O:27])[CH2:19]2)=O)=[CH:10][CH:9]=1.Cl>CO>[F:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15]([CH3:42])([CH3:41])[CH2:16][N:18]2[CH2:23][CH2:22][CH2:21][CH:20]([CH2:24][NH:25][C:26]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]4[N:39]([CH3:40])[N:38]=[N:37][N:36]=4)[CH:30]=3)=[O:27])[CH2:19]2)=[CH:10][CH:9]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 8028TetrahydrofuranHCID 697363521-{1-[3-(4-fluorophenyl)-2,2-dimethylpropionyl]-piperidin-3-ylmethyl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea

生成物 1

HCID 99130081-{1-[3-(4-Fluorophenyl)-2,2-dimethylpropyl]-piperidin-3-ylmethyl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea収率 38%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

A solution of borane in tetrahydrofuran (1.0 M, 5.3 mL, 5.3 mmol) was added to 1-{1-[3-(4-fluorophenyl)-2,2-dimethylpropionyl]-piperidin-3-ylmethyl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea (66 mg, 134 μmol) and the resulting solution was stirred at room temperature for 18 hours. A mixture of 1.0 N hydrochloric acid (5 mL) and methanol (5 mL) was added very slowly until the resulting vigorous reaction subsided, then the remainder was added quickly and the resulting solution was stirred at room temperature for 5 hours. The solution was concentrated under vacuum. The residue was dissolved in 1.0 N aqueous sodium hydroxide and dichloromethane, and the phases were separated. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were dried over sodium sulfate and concentrated under vacuum. The residue was purified twice by flash chromatography, eluting with 4% methanol in dichloromethane containing 0.4% aqueous ammonium hydroxide, to provide a white amorphous solid (24 mg, 38%). 1H NMR (300 MHz, CDCl3) δ7.81 (s, 1H), 7.68 (d, J=8 Hz, 1H), 7.34 (t, J=8 Hz, 1H), 7.18 (m, 1H), 7.01 (m, 2H), 6.84 (t, J=9 Hz, 2H), 4.09 (s, 3H), 3.09 (m, 2H), 2.95 (m, 1H), 2.55 (s, 2H), 2.40 (m, 3H), 2.10 (m, 1H), 1.9-1.5 (m, 5H), 1.0 (m, 1H), 0.85 (s, 6H). Mass spec (ES+) m/z 480.5 (M+H+).

後処理

  1. additionwas added very slowly until the resulting vigorous reaction
  2. additionthe remainder was added quickly
  3. stirringthe resulting solution was stirred at room temperature for 5 hours
  4. concentrationThe solution was concentrated under vacuum
  5. dissolutionThe residue was dissolved in 1.0 N aqueous sodium hydroxide
  6. customdichloromethane, and the phases were separated
  7. extractionThe aqueous phase was extracted twice with dichloromethane
  8. dry with materialthe combined organic phases were dried over sodium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified twice by flash chromatography
  11. washeluting with 4% methanol in dichloromethane containing 0.4% aqueous ammonium hydroxide

出典と根拠

ORDレコード
ord-a1367abda6d946648213a758ce652f4b
出典データセット
uspto-grants-2005_07
特許番号
US06919356B2

反応ノート

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