Acetone Cyanohydrin → HCID 178495761, compound

HRID 714429Notes

Reaction equation

HRID 714429 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[C:10](=[O:11])[C:9]([C:12]([OH:14])=O)=[CH:8][N:7]=[C:6]1[C:15]1[CH:19]=[CH:18][S:17][CH:16]=1.C(Cl)(=O)C(Cl)=O.[C:26]1(=[O:33])[CH2:31][CH2:30][CH2:29][C:28](=[O:32])[CH2:27]1.C(N(CC)CC)C.OC(C)(C)C#N>ClCCl.CN(C)C=O>[OH:33][C:26]1[CH2:31][CH2:30][CH2:29][C:28](=[O:32])[C:27]=1[C:12]([C:9]1[C:10](=[O:11])[N:5]([CH2:4][CH2:3][O:2][CH3:1])[C:6]([C:15]2[CH:19]=[CH:18][S:17][CH:16]=2)=[N:7][CH:8]=1)=[O:14]

Participants

8

Reactant 5

HCID 6406Acetone CyanohydrinHCID 8471Triethylamine2×HCID 104341,3-CyclohexanedioneHCID 65578Oxalyl chlorideHCID 679551311,6-Dihydro-1-(2-methoxyethyl)-6-oxo-2-(3-thienyl)-5-pyrimidinecarboxylic acid2×

Product 1

HCID 178495761HCID 178495761, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To 1,6-dihydro-1-(2-methoxyethyl)-6-oxo-2-(3-thienyl)-5-pyrimidinecarboxylic acid (i.e. the product from Example 10, Step C) (0.5 g, 1.8 mmol) in 10 mL of dichloromethane was added oxalyl chloride (0.45 g, 3.6 mmol) and one drop of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure. The crude oil was redissolved in 10 mL of dichloromethane and treated with 1,3-cyclohexanedione (0.22 g, 2.0 mmol) and triethylamine (0.18 g, 1.8 mmol). The reaction mixture was stirred for 30 min then treated with a catalytic amount of 2-hydroxy-2-methyl-propanenitrile (0.015 g, 0.18 mmol) and triethylamine (0.182 g, 1.8 mmol) and stirred at ambient temperature for 16 h. The reaction mixture was then concentrated under reduced pressure and purified by medium pressure liquid chromatography on silica gel eluting with 0 to 10% methanol in chloroform to provide 0.160 g of the title compound (also known as 2-[[1,6-dihydro-1-(2-methoxyethyl)-6-oxo-2-(3-thienyl)-5-pyrimidinyl]carbonyl]-1,3-cyclohexanedione), a compound of the invention, as a solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe crude oil was redissolved in 10 mL of dichloromethane
  3. stirringThe reaction mixture was stirred for 30 min
  4. stirringstirred at ambient temperature for 16 h
  5. concentrationThe reaction mixture was then concentrated under reduced pressure
  6. custompurified by medium pressure liquid chromatography on silica gel eluting with 0 to 10% methanol in chloroform

Sources & evidence

ORD record
ord-a05b51d4f77d497196669a6f112aa035
Source dataset
uspto-grants-2015_11
Patent number
US09187432B2

Reaction notes

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