Acrylonitrile → HCID 90402665, compound

HRID 2200645Notes

Reaction equation

HRID 2200645 reaction equation
[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[NH:13][C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:29])[F:28])[CH:21]=2)=[CH:4][CH:3]=1.C1COCC1.C[CH2:39][CH2:40][CH2:41][N+:42](CCCC)(CCCC)CCCC.[OH-].C(#N)C=C>C(Cl)Cl.O.C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:39][CH2:40][C:41]#[N:42])[C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:28])[F:29])[CH:21]=2)=[CH:31][CH:32]=1

Participants

8

Reactant 4

HCID 7855AcrylonitrileHCID 8028TetrahydrofuranHCID 2723671Tetrabutylammonium HydroxideHCID 90403003HCID 90403003, compound2×

Product 1

HCID 90402665HCID 90402665, compoundYield 74.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 7-(4-chlorobenzyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (100 mg, 0.215 mmol, Intermediate 9) in a mixed solution of THF (3 mL) and acetonitrile (5 mL) was added TBAH (0.05 ml, 0.193 mmol) and acrylonitrile (40 mg, 0.642 mmol). The mixture was stirred at 60° C. overnight. Then the mixture was diluted with DCM and water, and the phases were separated. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give crude product. This crude material was purified by silica gel chromatography eluting with petroleum/ethyl acetate (3:1 to 1:1) to give 3-(7-(4-chlorobenzyl)-3-methyl-2,6-dioxo-8-(3-(trifluoromethoxy)phenoxy)-2,3,6,7-tetrahydro-1H-purin-1-yl)propanenitrile (75 mg, 68.8%) as white solid. 1H-NMR (DMSO-d6) δ 7.63-7.59(t, 1H), 7.50(s, 1H), 7.45-7.40(m, 5H), 7.35-7.33(d, 1H), 5.45(s, 2H), 4.16-4.13(t, 2H), 3.31(s, 3H), 2.89-2.86(t, 2H). LCMS retention time 3.248 min; LCMS MH+ 520.

Workup

  1. customthe phases were separated
  2. washThe organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give crude product
  7. customThis crude material was purified by silica gel chromatography
  8. washeluting with petroleum/ethyl acetate (3:1 to 1:1)

Sources & evidence

ORD record
ord-3b26897d33454b5d93d5b705b22486bc
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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