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

HRID 2268962
Notes
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Reaction equation

HRID 2268962 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 101863Phosphorochloridic acid, dimethyl esterHCID 183326302-[1-(Piperidin-3-yl)-ethylamino]-4-[benzimidazol-1-yl]pyrimidine

Product 1

HCID 701386792-[1-(1-Dimethylphosphonopiperidin-3-yl)-ethylamino]-4-[benzimidazol-1-yl]-pyrimidineYield 69.4%

Reagents, catalysts & solvents 2

HCID 6344
Dichloromethane
Solvent
HCID 8857Ethyl AcetateSolvent

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

  1. washwas washed with saturated aqueous NaHCO3
  2. dry with materialThe organic layer was dried over Na2SO4
  3. customAfter removal of the solvent
  4. 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

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes