Water → 5-[(3-Hydroxypropyl)thio]-3-methyl-1-(2-methylpropyl)-6-[(pyridin-3-yl)carbonyl]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 379586Notes

Reaction equation

HRID 379586 reaction equation
[H-].[Na+].[SH:3][CH2:4][CH2:5][CH2:6][OH:7].Br[C:9]1[C:17]2[C:16](=[O:18])[N:15]([CH3:19])[C:14](=[O:20])[N:13]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:12]=2[S:11][C:10]=1[C:25]([C:27]1[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=1)=[O:26].O>O1CCCC1>[OH:7][CH2:6][CH2:5][CH2:4][S:3][C:9]1[C:17]2[C:16](=[O:18])[N:15]([CH3:19])[C:14](=[O:20])[N:13]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:12]=2[S:11][C:10]=1[C:25]([C:27]1[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=1)=[O:26]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 882113-MercaptopropanolHCID 183665815-bromo-3-methyl-1-(2-methylpropyl)-6-[(pyridin-3-yl)carbonyl]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 98029245-[(3-Hydroxypropyl)thio]-3-methyl-1-(2-methylpropyl)-6-[(pyridin-3-yl)carbonyl]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 56.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (0.068 g) in dry tetrahydrofuran (25 ml) was added dropwise a solution of 3-mercaptopropanol (0.14 g) in dry tetrahydrofuran (5 ml). After 15 minutes, a solution of 5-bromo-3-methyl-1-(2-methylpropyl)-6-[(pyridin-3-yl)carbonyl]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (0.60 g, Example 39 step c) in dry tetrahydrofuran (20 ml) was added dropwise and the reaction was stirred for 3 hours at room temperature. The solution was poured into water and extracted with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal-phase HPLC eluting with a gradient of 0-5% ethanol in dichloromethane to give the title compound as a cream solid (0.35 g).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by normal-phase HPLC
  6. washeluting with a gradient of 0-5% ethanol in dichloromethane

Sources & evidence

ORD record
ord-62787f83a5b0451995500215477c0392
Source dataset
uspto-grants-2001_10
Patent number
US06300334B1

Reaction notes

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