Sodium hydride → 4-[2-[[(1,3-benzodioxol-5-yl)methoxy]ethyl]piperidin-1-yl]-2-(1H-imidazol-1-yl)pyrimidine

HRID 352622

反応式

HRID 352622 の反応式
[N:1]1([C:6]2[N:11]=[C:10]([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]3[CH2:18][CH2:19][OH:20])[CH:9]=[CH:8][N:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].[CH2:23](Cl)[C:24]1[CH:32]=[CH:31][C:30]2[O:29][CH2:28][O:27][C:26]=2[CH:25]=1.[Cl-].C([NH3+])(C)(C)C>CN(C=O)C>[O:29]1[C:30]2[CH:31]=[CH:32][C:24]([CH2:23][O:20][CH2:19][CH2:18][CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17][N:12]3[C:10]3[CH:9]=[CH:8][N:7]=[C:6]([N:1]4[CH:5]=[CH:4][N:3]=[CH:2]4)[N:11]=3)=[CH:25][C:26]=2[O:27][CH2:28]1

参加物

6

反応物 4

HCID 24758Sodium hydrideHCID 887131,3-Benzodioxole, 5-(chloromethyl)-HCID 11355454t-Butylammonium chlorideHCID 224879671-[(1H-imidazol-1-yl)pyrimidin-4-yl]piperidine-2-ethanol

生成物 1

HCID 229583294-[2-[[(1,3-benzodioxol-5-yl)methoxy]ethyl]piperidin-1-yl]-2-(1H-imidazol-1-yl)pyrimidine収率 35%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

The above synthesis may be carried out as follows: To DMF (100 ml) was added 4-chloro-2-imidazol-1-ylpyrimidine (0.50 g, 2.77 mmol), 2-piperidineethanol (0.359 g, 2.77 mmol), and Hünig's base (0.536 g, 4.15 mmol). After heating at 80° C. for 5 hours, the solvent was removed in vacuo and the residue was chromatographed (CH2Cl2/MeOH, 19/1) to give 349 mg (46%) of 1-[(1H-imidazol-1-yl)pyrimidin-4-yl]piperidine-2-ethanol (the compound of formula (XVI)), (1H NMR (CDCl3) δ8.54 (s, 2), 8.11 (d, 1), 7.82 (t, 1), 7.11 (d, 1), 6.44 (d, 1), 3.60 (m, 2), 3.03 (m, 1), 1.77 (m); MS: 2.74 (M+H)+). To a solution of 1-[(1H-imidazol-1-yl)pyrimidin-4-yl]piperidine-2-ethanol (25 mg, 0.092 mmol) dissolved in DMF (5 ml) was added NaH (60% dispersion in oil, 5.5 mg, 0.14 mmol) followed by piperonyl chloride (17 mg, 0.10 mmol) and t-butyl ammonium chloride. After stirring for 16 hours at 80° C., the solvent was removed in vacuo and the residue was partitioned with saturated NH4Cl and CH2Cl2. The organic layer was separated, dried (MgSO4), the solvent removed in vacuo, and the residue chromatographed (CH2Cl2/MeOH, 19/1) to give 13 mg (35%) of 4-[2-[[(1,3-benzodioxol-5-yl)methoxy]ethyl]piperidin -1-yl]-2-(1H-imidazol-1-yl)pyrimidine (the compound of formula (Icc)); 1H NMR (CDCl3) δ8.52 (s, 1), 8.05 (d, 1), 7.80 (s, 1), 7.09 (s, 1), 6.73 (m, 3), 6.45 (d, 1), 5.93 (s, 2), 4.30 (s, 2), 3.45 (m, 2),2.95 (m, 1), 1.55 (m); MS: 408.7 (M+H)+.

後処理

  1. customthe solvent was removed in vacuo
  2. customthe residue was partitioned with saturated NH4Cl and CH2Cl2
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customthe residue chromatographed (CH2Cl2/MeOH, 19/1)

出典と根拠

ORDレコード
ord-45907608ec5d4de0b23b7074636998f2
出典データセット
uspto-grants-2004_06
特許番号
US06747031B2

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