Acetonitrile → 6-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido(4,3-d)pyrimidine

HRID 535344Notes

Reaction equation

HRID 535344 reaction equation
[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][NH:14][C:15](=O)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:21])=O.C(#N)C.C(=O)(O)[O-].[Na+]>ClCCl.CN(C=O)C>[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][N:14]=[C:15]([Cl:21])[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 1355929356-benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4(3H)-one

Product 1

HCID 253240466-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido(4,3-d)pyrimidineYield 57.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 6-benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4(3H)-one (5.0 g, 0.02 mol), phosphoryl chloride (3.30 mL, 0.035 mol) and acetonitrile (80 mL) and DMF (catalytic amount) was heated to at 70° C. for 1 hour. The mixture was reduced in vacuo and the remaining black residue was taken up in dichloromethane (250 ml) and poured over ice. The mixture was carefully neutralized with the addition of solid sodium bicarbonate. The layers were separated and the organic dried over sodium sulfate and reduced in vacuo. The mixture was chromatographed using an ethyl acetate:hexanes (0-100%) gradient on an isco flash chromatography system. The combined pure fractions were reduced in vacuo to yield the title compound as a yellow oil (3 g, 57.8%).

Workup

  1. additionpoured over ice
  2. customThe layers were separated
  3. dry with materialthe organic dried over sodium sulfate
  4. customThe mixture was chromatographed

Sources & evidence

ORD record
ord-9e79badb54384c4dae4aae877b5eeaf3
Source dataset
uspto-grants-2014_10
Patent number
US08859545B2

Reaction notes

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