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Diisopropylamine → [4-((3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidin-1-yl]-imidazol-1-yl-methanone

HRID 1592587
ノート
印刷プレビュー

反応式

HRID 1592587 の反応式
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:23]([C:24]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)([CH3:26])[CH3:25])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[C:34](N1C=CN=C1)([N:36]1[CH:40]=[CH:39][N:38]=[CH:37]1)=[O:35].C(NC(C)C)(C)C>C1COCC1.CN(C=O)C>[NH4+:4].[OH-:35].[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:23]([C:24]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)([CH3:26])[CH3:25])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:11]2[CH2:12][CH2:13][N:14]([C:34]([N:36]3[CH:40]=[CH:39][N:38]=[CH:37]3)=[O:35])[CH2:15][CH2:16]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 7912DiisopropylamineHCID 682631,1'-CarbonyldiimidazoleHCID 58997004(3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-piperidin-4-yl-amine

生成物 2

HCID 14923Ammonium HydroxideHCID 58997016[4-((3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidin-1-yl]-imidazol-1-yl-methanone
収率 53.6%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

(3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-piperidin-4-yl-amine (0.270 g, 0.60 mmol) and 1,1′-carbonyldiimidazole (0.098 g, 0.60 mmol) were combined in THF (6 mL) and the mixture was stirred at room temperature for one hour. The solvent was removed under reduced pressure to give a colorless oil that was resuspended in DMF (5 mL), followed by addition of N,N-diisopropylamine (527 μL, 3.02 mmol) and NH2OHHCl (0.168 g, 2.40 mmol). The mixture was stirred at room temperature for 16 hours and then the solvent was removed under reduced pressure. The yellow oil was resuspended in CH2Cl2 (30 mL), washed with brine (3×20 mL) and the organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give a yellow oil. Purification by column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 85:10:5, v/v/v) afforded COMPOUND 318 as a white foamy solid (0.087 g, 27%). 1H NMR (CDCl3) δ 1.29-1.42 (m, 2H), 1.62 (s, 6H), 1.76 (d, 2H, J=12.0 Hz), 2.22 (s, 3H), 2.29 (s+m, 4H), 2.75-2.84 (m, 3H), 3.42 (m, 1H), 3.71 (br s, 2H), 4.02 (d, 2H, J=12.0 Hz), 6.87 (t, 2H, J=9.0 Hz), 7.07 (s, 2H), 7.15 (s, 1H), 7.23 (s, 1H), 7.23 (s, 1H), 7.81 (s, 1H), 7.88 (m, 1H), 8.15 (s, 1H), 8.54 (s, 1H). 13C NMR (CDCl3) δ 17.9, 18.2, 28.2, 31.0, 42.1, 46.3, 54.2, 115.0, 115.3, 118.0, 127.3, 129.6, 132.6, 136.9, 146.5, 150.7, 159.3. HPLC: 91%. ES-MS m/z 541 [M+H]+. Anal. Calcd. for C32H37N6OF.0.15 CH2Cl2: C, 69.78; H, 6.79; N, 15.19. Found: C, 69.74; H, 6.83; N, 15.03.

後処理

  1. customThe solvent was removed under reduced pressure
  2. customto give a colorless oil that
  3. stirringThe mixture was stirred at room temperature for 16 hours
  4. customthe solvent was removed under reduced pressure
  5. washwashed with brine (3×20 mL)
  6. dry with materialthe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a yellow oil
  10. customPurification by column chromatography on silica gel (CH2Cl2

出典と根拠

ORDレコード
ord-1c699eb8aa734af686347c215c2d12bf
出典データセット
uspto-grants-2007_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07291631B2

反応ノート

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