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

HRID 434237

Reaction equation

[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

Participants

Conditions

Temperature: 80 °C

Procedure

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)+.

Workup

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

Sources & evidence

ORD record: ord-89f043889a2548508fc06e5dcc7976dd
Source dataset: uspto-grants-2003_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06670473B2

Linked notes

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