Triethylamine → (R)-1-[4-(2-methyl-4-phenyl-5,8-dihydro-6H-pyrido[3,4-d]pyrimidin-7-yl)-pyrimidin-2-yl]-ethyl butyrate

HRID 586171Notes

Reaction equation

HRID 586171 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:5]2[CH2:11][CH2:10][NH:9][CH2:8][C:6]=2[N:7]=1.[C:18]([O:23][C@@H:24]([C:26]1[N:31]=[C:30](Cl)[CH:29]=[CH:28][N:27]=1)[CH3:25])(=[O:22])[CH2:19][CH2:20][CH3:21].C(N(CC)CC)C>C(O)(C)C>[C:18]([O:23][C@@H:24]([C:26]1[N:27]=[C:28]([N:9]2[CH2:10][CH2:11][C:5]3[C:4]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)=[N:3][C:2]([CH3:1])=[N:7][C:6]=3[CH2:8]2)[CH:29]=[CH:30][N:31]=1)[CH3:25])(=[O:22])[CH2:19][CH2:20][CH3:21]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10944226(R)-1-(4-chloro-pyrimidin-2-yl)ethyl butyrateHCID 223286242-Methyl-4-phenyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine

Product 1

HCID 53875213(R)-1-[4-(2-methyl-4-phenyl-5,8-dihydro-6H-pyrido[3,4-d]pyrimidin-7-yl)-pyrimidin-2-yl]-ethyl butyrateYield 88%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of 2-methyl-4-phenyl-5,8-dihydro-6H-pyrido[3,4-d]pyrimidine (prepared according to the method of Example 86, Step D, 6.8 g, 30.0 mmol) in isopropanol (125 mL) was added (R)-1-(4-chloro-pyrimidin-2-yl)-ethyl butyrate (prepared according to the method of Preparation Seven, 6.8 g, 30 mmol) followed by triethylamine (12.5 mL, 89.9 mmol). This mixture was stirred at reflux for 8 h, cooled to room temperature overnight, and evaporated. The residue was diluted with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic extracts were dried over sodium sulfate, filtered, evaporated, and purified by flash column chromatography (2% methanol/ethyl acetate) to give 11.0 g (88%) of the title compound of Example 86, Step E, as a yellow oil. 1H NMR (CDCl3, 250 MHz) δ 8.28 (d, 1H), 7.62-7.40 (c, 5H), 6.45 (d, 1H), 5.69 (q, 1H), 4.78 (s, 2H), 3.93 (app s, 2H), 2.95 (t, 2H), 2.77 (s, 3H), 2.40 (t, 2H), 1.77-1.63 (c, 2H), 1.60 (d, 3H), 0.98 (t, 3H); MS (APCI) 418 (MH+).

Workup

  1. customprepared
  2. customaccording to the method of Preparation Seven, 6.8 g, 30 mmol)
  3. temperatureat reflux for 8 h
  4. customevaporated
  5. additionThe residue was diluted with saturated aqueous sodium bicarbonate
  6. extractionextracted with ethyl acetate (3×)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. custompurified by flash column chromatography (2% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-667f76d6ee4e444e821c68c876b6419e
Source dataset
uspto-grants-2005_08
Patent number
US06936600B2

Reaction notes

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