4-Quinolinecarboxaldehyde → Ethyl 1,2,3,4-tetrahydro-6-(hydroxy-4-quinolinylmethyl)-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylate

HRID 131552

Reaction equation

HRID 131552 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH3:9][N:10]1[C:15](=[O:16])[C:14]2[C:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][S:19][C:13]=2[N:12]([CH2:25][CH:26]([CH3:28])[CH3:27])[C:11]1=[O:29].[N:30]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:33]([CH:40]=[O:41])=[CH:32][CH:31]=1>C1COCC1>[OH:41][CH:40]([C:33]1[C:34]2[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=2)[N:30]=[CH:31][CH:32]=1)[C:18]1[S:19][C:13]2[N:12]([CH2:25][CH:26]([CH3:28])[CH3:27])[C:11](=[O:29])[N:10]([CH3:9])[C:15](=[O:16])[C:14]=2[C:17]=1[C:20]([O:22][CH2:23][CH3:24])=[O:21]

Participants

5

Reactant 3

HCID 780724-QuinolinecarboxaldehydeHCID 2724682Lithium diisopropylamideHCID 5282568Ethyl 3-methyl-1-(2-methylpropyl)-2,4-dioxo-1,2,3,4-tetrahydro-thieno[2,3-d]pyrimidine-5-carboxylate

Product 1

HCID 5282569Ethyl 1,2,3,4-tetrahydro-6-(hydroxy-4-quinolinylmethyl)-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of lithium diisopropylamide (5.52 g) in anhydrous THF (80 ml) was added dropwise over 1 h to a stirred solution of the product of step c) (8.02 g) and 4-quinolinecarboxaldehyde (8.12 g) in anhydrous THF (80 ml) at −78° C. under nitrogen. The mixture was stirred for a further 1 hour at −78° C. then quenched with glacial acetic acid (10 ml), allowed to warm to room temperature, diluted with saturated sodium bicarbonate solution (100 ml) and extracted into ethyl acetate (2×100 ml). The combined extracts were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography, eluting with 3:2 ethyl acetate/i-hexane, to give the sub-title compound as a white solid (7.35 g). MS(ESI) 468 {M+H]+. δ 1HCDCl3 0.85 (3H,d), 0.88 (3H,d), 1.43 (3H,t), 2.10-2.16 (1H,m), 3.38 (3H,s), 3.49 (1H,dd), 3.61 (1H, s,br), 3.71 (1H,dd), 4.48 (2H,quartet), 6.78 (1H,s), 7.52 (1H,t), 7.72 (1H,t), 7.83 (1H,d), 7.90 (1H,d), 8.17 (1H,d), 9.02 (1H,d)

Workup

  1. customthen quenched with glacial acetic acid (10 ml)
  2. temperatureto warm to room temperature
  3. additiondiluted with saturated sodium bicarbonate solution (100 ml)
  4. extractionextracted into ethyl acetate (2×100 ml)
  5. dry with materialThe combined extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography
  9. washeluting with 3:2 ethyl acetate/i-hexane

Sources & evidence

ORD record
ord-be19efb468db49dab3ea2944cc2e8b92
Source dataset
uspto-grants-2008_06
Patent number
US07384950B2

Linked notes

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