Sodium Methoxide → Allyl trans-2-[3-(6-chloro-3,4-dihydro-4-oxothieno[3,2-d]pyrimidin-3-yl)-2-oxopropyl]-3-methoxy-1-piperidinecarboxylate

HRID 4271Notes

Reaction equation

HRID 4271 reaction equation
[Cl:1][C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][CH:6]=[N:5][C:4]=2[CH:3]=1.C[O-].[Na+].[CH3:15][O:16][C@@H:17]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][CH2:26][CH:27]=[CH2:28])=[O:24])[C@H:18]1[CH2:29][C:30](=[O:33])[CH2:31]Br>CO>[Cl:1][C:2]1[S:10][C:9]2[C:8](=[O:11])[N:7]([CH2:31][C:30](=[O:33])[CH2:29][C@H:18]3[C@H:17]([O:16][CH3:15])[CH2:22][CH2:21][CH2:20][N:19]3[C:23]([O:25][CH2:26][CH:27]=[CH2:28])=[O:24])[CH:6]=[N:5][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 86741991Allyl trans-2-(3-bromo-2-oxopropyl)-3-methoxy-1-piperidinecarboxylateHCID 1355834876-chlorothieno[3,2-d]pyrimidin-4(3H)-one

Product 1

HCID 70393804Allyl trans-2-[3-(6-chloro-3,4-dihydro-4-oxothieno[3,2-d]pyrimidin-3-yl)-2-oxopropyl]-3-methoxy-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Under a nitrogen atmosphere in a flame dried flask and with magnetic stirring, a solution of 0.80 g (0.0043 mole) of 6-chlorothieno[3,2-d]pyrimidin-4(3H)-one, 3.52 ml of 1.22N sodium methoxide in methanol, and 20 ml of methanol was treated with 1.86 g (0.0056 mole) of allyl trans-3-methoxy-2-(3-bromo-2-oxopropyl)-1-piperidinecarboxylate. The reaction mixture was stirred overnight at room temperature, and was then evaporated under reduced pressure. The residue was taken up in 25 ml of 0.1N aqueous sodium hydroxide, and the resulting solution was extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate, filtered, and evaporated to afford a solid material which was chromatographed under moderate pressure ("flash" chromatography) on a column of silica gel (Woelm 32-63 micrometers, i.d. 2 cm×height 25 cm); the eluant was 7% ethanol in chloroform; after a forerun of 125 ml, 25 ml fractions were taken. Fractions 13-20 were combined and evaporated to furnish the title compound: yield 0.56 g (27%); 1H-nmr (CDCl3) delta ppm 1.2-2.1 (multiplet, 4H, OCHCH2CH2CH2N), 2.7-3.1 (multiplet, peaks, 4H, COCH2CH and NCH2), 3.3 (broad singlet, 1H, CH2CHNCO), 3.4 (singlet, 3H, OCH3), 4.0 (broad doublet, 1H, CHOCH3), 4.6 (broad double, 2H, CH2CH=CH2), 4.8-5.1 (multiple peaks, 2H, NCH2CO), 5.3 (triplet with fine splitting, 2H, CH2 =CH), 5.9 (octet, 1H, CH=CH2), 7.2 (singlet, 1H, thieno H), 8.0 (broad singlet, 1H, N=CH--N).

Workup

  1. customUnder a nitrogen atmosphere in a flame dried flask
  2. customwas then evaporated under reduced pressure
  3. extractionthe resulting solution was extracted with dichloromethane
  4. dry with materialThe extract was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto afford a solid material which
  8. customwas chromatographed under moderate pressure ("flash" chromatography) on a column of silica gel (Woelm 32-63 micrometers, i.d. 2 cm×height 25 cm)
  9. customevaporated

Sources & evidence

ORD record
ord-28268398841145ef80593572bb765ce9
Source dataset
uspto-grants-1988_02
Patent number
US04725599

Reaction notes

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