Sodium Cyanide → HCID 118599079, compound

HRID 1050381Notes

Reaction equation

HRID 1050381 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11](NC(C3CC3)=O)[CH:10]=2)[C:5](=[O:21])[N:4]2[C:22]([C:27]3C=CC=C(F)C=3)([CH3:26])[NH:23][C:24](=[O:25])[C:3]=12.[Cu][C:35]#[N:36].[C-]#N.[Na+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:26][C:22]1([CH3:27])[N:4]2[C:5](=[O:21])[C:6]([NH:8][C:9]3[CH:10]=[CH:11][N:12]=[CH:13][N:14]=3)=[CH:7][C:2]([C:35]#[N:36])=[C:3]2[C:24](=[O:25])[NH:23]1

Participants

7

Reactant 4

HCID 8929Sodium CyanideHCID 75806TricyclohexylphosphineHCID 118598561HCID 118598561, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 118599079HCID 118599079, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a vial was added 8-chloro-3,3-dimethyl-6-(pyrimidin-4-ylamino)-2H-imidazo[1,5-c]pyridine-1,5-dione (1, 1000 mg, 3.27 mmol), copper(I) cyanide (293 mg, 3.27 mmol) and sodium cyanide (160 mg, 3.27 mmol) in 1,4-dioxane (10 mL) at room temperature under argon. The reaction was purged with argon for 5-10 min, followed by addition of tricyclohexylphosphine (92 mg, 0.33 mmol) and tris(dibenzylideneacetone)dipalladium(0) (299 mg, 0.33 mmol) under argon. The vial was then sealed and heated at 150° C. for 48 h. After completion the reaction was quenched with sat solution of potassium permanganate and extracted the crude compound with 10% methanol in dichloromethane. The organic layer was concentrated to dryness and crude was purified by flash column chromatography (silica gel 100-200 mesh) using 2% methanol in dichloromethane. The desired fractions were concentrated to dryness under vacuum to obtain 3,3-dimethyl-1,5-dioxo-6-(pyrimidin-4-ylamino)-2H-imidazo[1,5-a]pyridine-8-carbonitrile (Cpd. No. 181) as off white solid. Yield: 0.2 g, 20%; MS (ESI) m/z 297.36 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 9.69 (s, 1H), 8.90 (s, 1H), 8.85 (s, 1H), 8.44 (d, J=5.84 Hz, 1H), 7.44 (d, J=5.36 Hz, 1H), 1.82 (s, 6H).

Workup

  1. customThe reaction was purged with argon for 5-10 min
  2. customThe vial was then sealed
  3. customAfter completion the reaction was quenched with sat solution of potassium permanganate
  4. extractionextracted the crude compound with 10% methanol in dichloromethane
  5. concentrationThe organic layer was concentrated to dryness and crude
  6. customwas purified by flash column chromatography (silica gel 100-200 mesh)
  7. concentrationThe desired fractions were concentrated to dryness under vacuum

Sources & evidence

ORD record
ord-f48a5cb7a9a143d4b81b596bf3182d2d
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

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