Sodium Methoxide → Methyl trans-2-[3-(6,7-Dichloro-3,4-dihydro-4-oxothieno[3,2-d]pyrimidin-3-yl)-2-oxopropyl)-3-methoxy-1-piperidinecarboxylate

HRID 4268Notes

Reaction equation

HRID 4268 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[C:3]=1[Cl:12].C[O-].[Na+].[CH3:16][O:17][C@@H:18]1[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][CH3:27])=[O:25])[C@H:19]1[CH2:28][C:29](=[O:32])[CH2:30]Br.N1C2C=CS(=O)C=2C=NC=1>CO>[Cl:1][C:2]1[S:10][C:9]2[C:8](=[O:11])[N:7]([CH2:30][C:29](=[O:32])[CH2:28][C@H:19]3[C@H:18]([O:17][CH3:16])[CH2:23][CH2:22][CH2:21][N:20]3[C:24]([O:26][CH3:27])=[O:25])[CH:6]=[N:5][C:4]=2[C:3]=1[Cl:12]

Participants

6

Reactant 4

HCID 10942334Sodium MethoxideHCID 53628846ThienopyrimidinoneHCID 86741990Methyl trans-2-(3-bromo-2-oxopropyl)-3-methoxypiperidine-1-carboxylateHCID 1355834896,7-dichlorothieno[3,2-d]pyrimidin-4(3H)-one

Product 1

HCID 70393294Methyl trans-2-[3-(6,7-Dichloro-3,4-dihydro-4-oxothieno[3,2-d]pyrimidin-3-yl)-2-oxopropyl)-3-methoxy-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

Under nitrogen in a flame dried round bottom flask with magnetic stirring, a solution of 0.440 g (0.002 moles) of 6,7-dichlorothieno[3,2-d]pyrimidin-4(3H)-one [M. Robba, J- M. Lecomte, and M. Cugnon de Sevricourt, Bull. soc. chim. France, 1970, 3630-3636], 5 ml of methanol, and 2.0 ml of 1.0N sodium methoxide in methanol was treated with a solution of 0.002 moles of methyl trans-3-methoxy-2-(3-bromo-2-oxopropyl)-1-piperidinecarboxylate and 2 ml of methanol. A colorless precipitate formed almost immediately; the reaction mixture was stirred for two hours at room temperature. The solid matter was some starting thienopyrimidinone, and was filtered. The filtrate was evaporated under reduced pressure to afford a greenish oil which was chromatographed under moderate pressure ("flash" chromatography) on a column of silica gel (Woelm 32-63 micrometers, i.d. 5 cm×height 18 cm); the eluant was initially 1% ethanol in chloroform but was changed to 2% ethanol later on. There was obtained the title compound: m.p. 58°-62° C.; yield 0.270 g (30%); mass spectrum peaks at 447 (molecular ion), 415 (--32, --CH3OH), 195 (parent) among others; 13C-nmr delta (CDCl3) 19.05 ppm, 23.42, 39.33, 40.81, 50.53, 52.93, 53.62, 56.35, 76.01, 119.92, 121.68, 149.62, 152.19, 155.49, 157.01, 199.22; 1H-nmr (CDCl3) delta 3.36 ppm (OCH3), 3.66 (CO2CH3) among others.

Workup

  1. customUnder nitrogen in a flame dried round bottom flask with magnetic stirring
  2. customA colorless precipitate formed almost immediately
  3. filtrationwas filtered
  4. customThe filtrate was evaporated under reduced pressure
  5. customto afford a greenish oil which
  6. customwas chromatographed under moderate pressure ("flash" chromatography) on a column of silica gel (Woelm 32-63 micrometers, i.d. 5 cm×height 18 cm)

Sources & evidence

ORD record
ord-1c1a49e7765a4431bc8ffdded835f413
Source dataset
uspto-grants-1988_02
Patent number
US04725599

Reaction notes

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