1-Ethylpiperazine → Methyl 4-chloro-2-(4-ethylpiperazin-1-yl)-6-(m-tolylamino)pyrimidine-5-carboxylate

HRID 2092736Notes

Reaction equation

HRID 2092736 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([O:11][CH3:12])=[O:10])=[C:4]([NH:13][C:14]2[CH:15]=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=2)[N:3]=1.C(N(C(C)C)C(C)C)C.[CH2:30]([N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)[CH3:31].C([O-])(O)=O.[Na+]>C1COCC1>[Cl:8][C:6]1[C:5]([C:9]([O:11][CH3:12])=[O:10])=[C:4]([NH:13][C:14]2[CH:15]=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=2)[N:3]=[C:2]([N:35]2[CH2:36][CH2:37][N:32]([CH2:30][CH3:31])[CH2:33][CH2:34]2)[N:7]=1

Participants

6

Reactant 4

HCID 791961-EthylpiperazineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 58317610Methyl 2,4-dichloro-6-(m-tolylamino)pyrimidine-5-carboxylate

Product 1

HCID 58317524Methyl 4-chloro-2-(4-ethylpiperazin-1-yl)-6-(m-tolylamino)pyrimidine-5-carboxylateYield 24.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 2,4-dichloro-6-(m-tolylamino)pyrimidine-5-carboxylate (502.6 mg, 1.610 mmol), N-ethyldiisopropylamine (0.3 mL, 1.718 mmol) and N-ethylpiperazine (0.21 mL, 1.653 mmol) in THF (8 mL) was stirred at RT for 12 h. Saturated aq NaHCO3 was added and the resulting mixture was extracted with EtOAc. The organic layers were washed with saturated aq NaHCO3, water, and brine, were dried over anhydrous Na2SO4, and then filtered through SiO2. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (SiO2, hexanes/EtOAc=4/1) to give the title compound (152.6 mg, 24%). 1H NMR (500 MHz, CDCl3) δ ppm 1.12 (t, J=6.5 Hz, 3H), 2.35 (s, 3H), 2.48 (br s, 6H), 3.82-3.97 (m, 7H), 6.92-6.93 (m, 1H), 7.21-7.22 (m, 1H), 7.37-7.42 (m, 2H), 10.45 (s, 1H). [M+H] calc'd for C19H25ClN5O2, 390. found, 390.

Workup

  1. extractionthe resulting mixture was extracted with EtOAc
  2. washThe organic layers were washed with saturated aq NaHCO3, water, and brine
  3. dry with materialwere dried over anhydrous Na2SO4
  4. filtrationfiltered through SiO2
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by column chromatography (SiO2, hexanes/EtOAc=4/1)

Sources & evidence

ORD record
ord-3b8bb0664493426bbb46f550a0d6eefb
Source dataset
uspto-grants-2013_05
Patent number
US08440689B2

Reaction notes

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