Triethylamine → (R)-1-[4-(4-Quinoxalin-2-yl-piperazin-1-yl)-pyrimidin-2-yl]-ethyl acetate

HRID 984879Notes

Reaction equation

HRID 984879 reaction equation
[C:1]([O:4][C@@H:5]([C:7]1[N:12]=[C:11](Cl)[CH:10]=[CH:9][N:8]=1)[CH3:6])(=[O:3])[CH3:2].C(N(CC)CC)C.[N:21]1([C:27]2[CH:36]=[N:35][C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[N:28]=2)[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>C(O)(C)C>[C:1]([O:4][C@@H:5]([C:7]1[N:12]=[C:11]([N:24]2[CH2:25][CH2:26][N:21]([C:27]3[CH:36]=[N:35][C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:28]=3)[CH2:22][CH2:23]2)[CH:10]=[CH:9][N:8]=1)[CH3:6])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 118205602-Piperazin-1-YL-quinoxalineHCID 54154993(R)-1-(4-chloropyrimidin-2-yl)-ethyl acetate

Product 1

HCID 10894166(R)-1-[4-(4-Quinoxalin-2-yl-piperazin-1-yl)-pyrimidin-2-yl]-ethyl acetateYield 91%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of (R)-1-(4-chloro-pyrimidin-2-yl)-ethyl acetate (prepared according to the method of Preparation Five, 7.3 g, 36.2 mmol) in isopropanol (240 mL) was added triethylamine (10.1 mL, 72.4 mmol) followed by 2-(1-piperazinyl)quinoxaline (10.1 g, 47.1 mmol; J. Med. Chem. 1981, 24, 93). This mixture was stirred at room temperature overnight then concentrated. The residue was diluted with saturated aqueous sodium bicarbonate and extracted with chloroform (5×). The combined organic extracts were dried over sodium sulfate, filtered, evaporated, and purified by flash column chromatography (2% methanol/chloroform) to give 12.4 g (91%) of the title compound of Example 1, Step A as a yellow foam. 1H NMR (CDCl3, 250 MHz) δ 8.61 (s, 1H), 8.27 (d, 1H), 7.91 (dd, 1H), 7.72 (dd, 1H), 7.61 (td, 1H), 7.44 (td, 1H), 6.43 (d, 1H), 5.70 (q, 1H), 3.96-3.84 (c, 8H), 2.18 (s, 3H), 1.61 (d, 3H); MS(CI/NH3) 379 (MH+).

Workup

  1. concentrationthen concentrated
  2. additionThe residue was diluted with saturated aqueous sodium bicarbonate
  3. extractionextracted with chloroform (5×)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by flash column chromatography (2% methanol/chloroform)

Sources & evidence

ORD record
ord-960b64a186734013b59072e9418f5a40
Source dataset
uspto-grants-2005_03
Patent number
US06869943B2

Reaction notes

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