Diisopropylamine → 5-[(3-Hydroxypropyl)sulfanyl]-1-isobutyl-3-methyl-6-(1-naphthylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 567890Notes

Reaction equation

HRID 567890 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH3:13][N:14]1[C:19](=[O:20])[C:18]2[CH:21]=[C:22]([CH2:24][C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=[CH:27][CH:26]=3)[S:23][C:17]=2[N:16]([CH2:35][CH:36]([CH3:38])[CH3:37])[C:15]1=[O:39].CC1C=C[C:44]([S:47](OCCCO[Si](C)(C)C(C)(C)C)(=O)=S)=[CH:43][CH:42]=1.[OH2:62].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.O>[OH:62][CH2:42][CH2:43][CH2:44][S:47][C:21]1[C:18]2[C:19](=[O:20])[N:14]([CH3:13])[C:15](=[O:39])[N:16]([CH2:35][CH:36]([CH3:37])[CH3:38])[C:17]=2[S:23][C:22]=1[CH2:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 5282538HCID 5282538, compoundHCID 162116731-Butanaminium, N,N,N-tributyl-, fluoride, hydrateHCID 53747051HCID 53747051, compoundHCID 178418339Butyllithium

Product 1

HCID 52825395-[(3-Hydroxypropyl)sulfanyl]-1-isobutyl-3-methyl-6-(1-naphthylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 39.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×

Procedure

Prepared according to the procedure described in Example 5 from n-butyllithium (2.0M solution in hexanes, 0.32 ml) and diisopropylamine (0.093 ml) in anhydrous tetrahydrofuran (5 ml), 3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (0.20 g) in anhydrous tetrahydrofuran (5 ml) and 3-{[dimethyl(1,1-dimethylethyl)silyl]oxy}propyl 4-methylphenylthiosulfonate (0.19 g, J. Med. Chem. 1995, 38, 2557) in anhydrous tetrahydrofuran (2 ml). The crude adduct was dissolved in tetrahydrofuran (6 ml) and treated with tetrabutylammonium fluoride hydrate (0.20 g). After 16 hours, the solution was diluted with water (30 ml) and extracted with ether (2×30 ml). The organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography over silica, eluting with ether and was then recrystallised from ethyl acetate/hexane to give the title compound (0.098 g).

Workup

  1. customPrepared
  2. extractionextracted with ether (2×30 ml)
  3. dry with materialThe organic extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography over silica
  7. washeluting with ether
  8. customwas then recrystallised from ethyl acetate/hexane

Sources & evidence

ORD record
ord-089a131601044cf4b4455581bf54bfcb
Source dataset
uspto-grants-2001_01
Patent number
US06180635B2

Reaction notes

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