Hydrochloric Acid → HCID 57445457, compound

HRID 422052Notes

Reaction equation

HRID 422052 reaction equation
F[C:2]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[NH:13][C:12](=[O:22])[N:11]=2)=[CH:6][C:3]=1[C:4]#[N:5].O.[NH2:24][NH2:25].CO.[ClH:28]>C(O)(C)(C)C.O1CCOCC1>[ClH:28].[ClH:28].[NH2:5][C:4]1[C:3]2[C:2](=[CH:9][CH:8]=[C:7]([C:10]3[CH:15]=[C:14]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[NH:13][C:12](=[O:22])[N:11]=3)[CH:6]=2)[NH:25][N:24]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 24654Hydrazine hydrate (1:1)HCID 66673053HCID 66673053, compound

Product 1

HCID 57445457HCID 57445457, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 312751,4-DioxaneSolvent

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. customwas used without further purification for the next step
  2. concentrationThe solution was concentrated in vacuo
  3. customto give a solid, which
  4. concentrationAfter concentration in vacuo
  5. customthe resultant solid was triturated in hot ethyl acetate
  6. filtrationcollected by vacuum filtration

Sources & evidence

ORD record
ord-f79f99adb2ce4a5f998208a2a6b85fd4
Source dataset
uspto-grants-2012_01
Patent number
US08101625B2

Reaction notes

Loading…