Triethylamine → 2-[1-(1-Dimethylphosphonopiperidin-3-yl)-ethylamino]-4-[benzimidazol-1-yl]-pyrimidine

HRID 2268962Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH2:2]1.C(N(CC)CC)C.[P:32](Cl)([O:36][CH3:37])([O:34][CH3:35])=[O:33]>C(Cl)Cl.CCOC(C)=O>[CH3:35][O:34][P:32]([N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH2:2]1)([O:36][CH3:37])=[O:33]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-[1-(piperidin-3-yl)-ethylamino]-4-[benzimidazol-1-yl]pyrimidine (EXAMPLE 18) (44 mg, 0.136 mmol) in CH2Cl2 (1.5 mL) was added triethylamine (29 μL, 0.204 mmol) followed by dimethyl chlorophosphate (22 μL, 0.204 mmol) at 0° C. After stirring 30 min at 0° C., the reaction mixture was diluted with EtOAc (10 mL) and was washed with saturated aqueous NaHCO3 followed by brine. The organic layer was dried over Na2SO4. After removal of the solvent, the crude product was purified by preparative thin layer chromatography (3:1 acetone:hexane) to obtain 40.6 mg of the title compound. Partial 1H NMR (500 MHz, CDCl3): δ 8.61 (s, 1H); 8.36 (br s, 1H); 8.14 (d, J=7.3 Hz, 1H); 7.83 (d, J=7.3 Hz, 1H); 7.38 (m, 2H); 6.78 (d, J=5.4 Hz, 1H); 4.15 (m, 1H); 3.67 (s, 3H); 3.65 (s, 3H); 1.28 (d, J=6.5 Hz, 3H). Mass spectrum 431.3 (ESI, M+1).

Workup

washwas washed with saturated aqueous NaHCO3
dry with materialThe organic layer was dried over Na2SO4
customAfter removal of the solvent
customthe crude product was purified by preparative thin layer chromatography (3:1 acetone:hexane)

Sources & evidence

ORD record: ord-11d3078afa6f454ca62ac06c036457be
Source dataset: uspto-grants-2001_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06329380B1

Reaction notes

Loading…