HCID 16661435, compound → HCID 66673053, compound

HRID 422051Notes

Reaction equation

HRID 422051 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[NH:12][C:11](=[O:21])[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[Cu][C:23]#[N:24]>CN(C)C=O>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[CH:14]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[NH:12][C:11](=[O:21])[N:10]=2)=[CH:3][C:2]=1[C:23]#[N:24]

Participants

4

Reactant 2

HCID 16661435HCID 16661435, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 66673053HCID 66673053, compoundYield 114.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(3-bromo-4-fluorophenyl)-6-phenylpyrimidin-2(1H)-one (0.3 g, 0.9 mmol) and copper(I) cyanide (0.16 g, 1.7 mmol) in N,N-dimethylformamide (3 mL) was heated to 155° C. for 24 hours. The crude reaction mixture was concentrated in vacuo then partitioned between saturated sodium bicarbonate (aqueous) and ethyl acetate/methanol (10:1). The layers were separated and the aqueous layer was extracted once with 10:1 ethyl acetate/methanol. The combined organic layers were dried (sodium sulfate), filtered and concentrated in vacuo to give 0.30 g (quantitative yield) of crude 2-fluoro-5-(2-oxo-6-phenyl-1,2-dihydropyrimidin-4-yl)benzonitrile that was used without further purification for the next step. A solution of 2-fluoro-5-(2-oxo-6-phenyl-1,2-dihydropyrimidin-4-yl)benzonitrile (0.30 g, 1.0 mmol) and hydrazine monohydrate (1.7 mL, 36 mmol) in t-butanol (34 mL) was heated at 120° C. for 12 hours. The solution was concentrated in vacuo to give a solid, which was taken into hot methyl alcohol and treated with an excess of 4.0M hydrogen chloride in dioxane. After concentration in vacuo, the resultant solid was triturated in hot ethyl acetate, collected by vacuum filtration then lyophilized from aqueous solution to give 4-(3-amino-1H-indazol-5-yl)-6-phenylpyrimidin-2(1H)-one dihydrochloride (0.034 g, 11% yield). 1H NMR (400 MHz, DMSO): 8.93 (broad s, 1H), 8.20 (d, 1H), 8.11 (d, 1H), 7.70 (t, 1H), 7.65 (t, 2H), 7.57 (broad s, 1H), 7.47 (d, 1H). MS (EI) for C17H13N5O: 304 (MH+).

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated in vacuo
  3. customthen partitioned between saturated sodium bicarbonate (aqueous) and ethyl acetate/methanol (10:1)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted once with 10:1 ethyl acetate/methanol
  6. dry with materialThe combined organic layers were dried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cfccf29d9e7e45ffab77bd28a5197ddd
Source dataset
uspto-grants-2012_01
Patent number
US08101625B2

Reaction notes

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