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

HRID 2227803Notes

Reaction equation

HRID 2227803 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) δ8.61 (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-bf64424d21554771a1e749a4616d9407
Source dataset
uspto-grants-2002_07
Patent number
US06414149B1

Reaction notes

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