Ammonium Chloride → 6[Hydroxy[6-(trifluoromethyl)-2-pyridinyl]methyl]-3-methyl-1-(2-methylpropyl)-5-(2-thienylthio)-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 379597Notes

Reaction equation

HRID 379597 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[N:8]=1.[CH3:17][N:18]1[C:23](=[O:24])[C:22]2[C:25]([S:30][C:31]3[S:32][CH:33]=[CH:34][CH:35]=3)=[C:26]([CH:28]=[O:29])[S:27][C:21]=2[N:20]([CH2:36][CH:37]([CH3:39])[CH3:38])[C:19]1=[O:40].[Li]C1C=CC=CN=1.[Cl-].[NH4+]>CCCCCC.O1CCCC1>[OH:29][CH:28]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[N:8]=1)[C:26]1[S:27][C:21]2[N:20]([CH2:36][CH:37]([CH3:39])[CH3:38])[C:19](=[O:40])[N:18]([CH3:17])[C:23](=[O:24])[C:22]=2[C:25]=1[S:30][C:31]1[S:32][CH:33]=[CH:34][CH:35]=1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 27829022-Bromo-6-(trifluoromethyl)pyridineHCID 183665901,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxo-5-(thien-2-ylthio)-thieno[2,3-d]pyrimidine-6-carboxaldehydeHCID 178418339ButyllithiumHCID 178506720HCID 178506720, compound

Product 1

HCID 101866156[Hydroxy[6-(trifluoromethyl)-2-pyridinyl]methyl]-3-methyl-1-(2-methylpropyl)-5-(2-thienylthio)-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

n-Butyl lithium in hexane (2.5M, 369 μl) was added dropwise to a solution of 2-bromo-6-trifluoromethylpyridine in tetrahydrofuran (8 ml) at −78° C. and the resulting solution was stirred for 1 h. 1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxo-5-(2-thienylthio)-thieno[2,3-d]pyrimidine-6-carboxaldehyde (0.25 g) (Example 50, step c) in tetrahydrofuran (2 ml) was added dropwise to the lithio pyridine solution. The reaction was stirred for 3 hours at −78° C. then saturated ammonium chloride solution was added (20 ml) and the reaction was left to warm to room temperature. The reaction was extracted thrice with ethyl acetate (50 ml), then the organic phases were washed with brine and dried over magnesium sulfate, filtered and evaporated to leave a brown oil. The residue was purified by chromatography (1:4, ethyl acetate: isohexane) to give the title compound as a pale brown oil (0.03 g).

Workup

  1. stirringThe reaction was stirred for 3 hours at −78° C.
  2. waitthe reaction was left
  3. extractionThe reaction was extracted thrice with ethyl acetate (50 ml)
  4. washthe organic phases were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto leave a brown oil
  9. customThe residue was purified by chromatography (1:4, ethyl acetate: isohexane)

Sources & evidence

ORD record
ord-246432ae8a2143ac89c7d1ec356022c8
Source dataset
uspto-grants-2001_10
Patent number
US06300334B1

Reaction notes

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