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

HRID 434237

반응식

HRID 434237 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

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) δ 8.54 (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: 274 (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) δ 8.52 (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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-89f043889a2548508fc06e5dcc7976dd
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06670473B2

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