Triethylamine → (R)-1-[4-(4-Oxazolo[5,4-b]pyridin-2-yl-piperazin-1-yl)-pyrimidin-2-yl]-ethyl butyrate

HRID 394507Notes

Reaction equation

HRID 394507 reaction equation
[C:1]([O:6][C@@H:7]([C:9]1[N:14]=[C:13](Cl)[CH:12]=[CH:11][N:10]=1)[CH3:8])(=[O:5])[CH2:2][CH2:3][CH3:4].C(N(CC)CC)C.[N:23]1([C:29]2[O:30][C:31]3[C:36]([N:37]=2)=[CH:35][CH:34]=[CH:33][N:32]=3)[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C(O)(C)C>[C:1]([O:6][C@@H:7]([C:9]1[N:14]=[C:13]([N:26]2[CH2:25][CH2:24][N:23]([C:29]3[O:30][C:31]4[C:36]([N:37]=3)=[CH:35][CH:34]=[CH:33][N:32]=4)[CH2:28][CH2:27]2)[CH:12]=[CH:11][N:10]=1)[CH3:8])(=[O:5])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10944226(R)-1-(4-chloro-pyrimidin-2-yl)ethyl butyrateHCID 223287892-Piperazin-1-yl[1,3]oxazolo[5,4-b]pyridine

Product 1

HCID 11143754(R)-1-[4-(4-Oxazolo[5,4-b]pyridin-2-yl-piperazin-1-yl)-pyrimidin-2-yl]-ethyl butyrateYield 94%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of (R)-1-(4-chloro-pyrimidin-2-yl)-ethyl butyrate (prepared according to the method of Preparation Seven, 6.8 g, 29.9 mmol) and triethylamine (12.5 mL, 89.6 mmol) in isopropanol (100 mL) was added 2-(1-piperazinyl)oxazolo[5,4-b]pyridine (prepared according to the method of Example 9, Step A, 6.1 g, 29.9 mmol). This mixture was stirred at reflux overnight, cooled to room temperature, and evaporated. The residue was diluted with saturated aqueous sodium bicarbonate and extracted with chloroform (3×). The combined organic extracts were dried over sodium sulfate, filtered, evaporated, and purified by flash column chromatography (1.5→2% methanol/chloroform) to give 11.1 g (94%) of the title compound of Example 9, Step B as a yellow oil which solidified upon standing. 1H NMR (CDCl3, 250 MHz) δ 8.28 (d, 1H), 7.97 (dd, 1H), 7.60 (dd, 1H), 7.25 (dd, 1H), 6.44 (d, 1H), 5.70 (q, 1H), 3.85 (app s, 8H), 2.42 (t, 2H), 1.78 -1.61 (c, 2H), 1.60 (d, 3H), 0.98 (t, 3H); MS (APCI) 397 (MH+).

Workup

  1. customprepared
  2. temperatureat reflux overnight
  3. customevaporated
  4. additionThe residue was diluted with saturated aqueous sodium bicarbonate
  5. extractionextracted with chloroform (3×)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. custompurified by flash column chromatography (1.5→2% methanol/chloroform)

Sources & evidence

ORD record
ord-bd1c5f02236c4040914e502d4c67a527
Source dataset
uspto-grants-2003_08
Patent number
US06602875B2

Reaction notes

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