HCID 11059510, compound → HCID 11045496, compound

HRID 1420298Notes

Reaction equation

HRID 1420298 reaction equation
[C:1]([Cu])#N.C[Li].[Cl:6][C:7]1[CH:12]=[C:11]([C:13]2[N:18]([CH2:19][C:20]#[CH:21])[C:17](=[O:22])[C:16]([CH2:23][CH3:24])=[C:15](OS(C(F)(F)F)(=O)=O)[N:14]=2)[CH:10]=[C:9]([Cl:33])[N:8]=1>C1COCC1>[Cl:6][C:7]1[CH:12]=[C:11]([C:13]2[N:18]([CH2:19][C:20]#[CH:21])[C:17](=[O:22])[C:16]([CH2:23][CH3:24])=[C:15]([CH3:1])[N:14]=2)[CH:10]=[C:9]([Cl:33])[N:8]=1

Participants

5

Reactant 3

HCID 11059510HCID 11059510, compoundHCID 178418348HCID 178418348, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 11045496HCID 11045496, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred, cold (-78° C.) solution of CuCN (1.91 g, 20 mmol) in 100 mL of THE was added methyllithium (30 mL, 42 mmol, 2.1 equiv, 1.4M in diethyl ether) over 10 min. After stirring for 15 min, this solution was added over 10 min via a canula to a cold (-78° C.) solution of 2-(2,6-dichloro-4-pyridyl)-5-ethyl-3-propargyl-6 -trifluoromethanesulfonyloxy-4(3H)-pyrimidinone in 20 mL of THF. The reaction mixture was stirred for 30 min, quenched with 15 mL of 10% concentrated NH4OH/saturated NH4Cl, diluted with 200 mL of ethyl acetate and warmed to room temperature. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were dried (MgSO4), filtered and concentrated to give a semi oil. The crude product was purified by flash chromatography (silica gel, ethyl acetate/hexane, 2/8) to afford 2.29 g (71%) of 2-(2,6-dichloro-4-pyridyl)-5-ethyl-6-methyl-3-propargyl-4(3H)-pyrimidinone as a white solid: mp 143°-144° C.; IR (KBr) 3220, 2125, 1668, 1584, 1541, 1515, 1367 cm-1 ; 1H NMR (270 MHz, CDCl3) δ 1.16 (t, J=7.6 Hz, 3H), 2.35 (s, 3H), 2.43 (t, J=2.6 Hz, 1H), 2.62 (q, J=14.8 Hz, 2H), 4.56 (d, J=2.6 Hz, 2H), 7.60 (s, 2H).

Workup

  1. stirringThe reaction mixture was stirred for 30 min
  2. customquenched with 15 mL of 10% concentrated NH4OH/saturated NH4Cl
  3. additiondiluted with 200 mL of ethyl acetate
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a semi oil
  10. customThe crude product was purified by flash chromatography (silica gel, ethyl acetate/hexane, 2/8)

Sources & evidence

ORD record
ord-c608206e3e094514aeb53de1e0b5ceea
Source dataset
uspto-grants-1999_03
Patent number
US05889184

Reaction notes

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