Sulfuric Acid → HCID 44546064, compound

HRID 1958657Notes

Reaction equation

HRID 1958657 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[NH:12][C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([CH3:32])[N:27]=3)=[C:14]([C:16]3[CH:17]=[C:18]4[C:23](=[CH:24][CH:25]=3)[N:22]=[CH:21][CH:20]=[N:19]4)[N:15]=2)=[CH:6][C:3]=1[C:4]#[N:5].[OH:33]S(O)(=O)=O.[NH4+].[OH-]>C(O)(=O)C.O>[F:1][C:2]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[NH:12][C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([CH3:32])[N:27]=3)=[C:14]([C:16]3[CH:17]=[C:18]4[C:23](=[CH:24][CH:25]=3)[N:22]=[CH:21][CH:20]=[N:19]4)[N:15]=2)=[CH:6][C:3]=1[C:4]([NH2:5])=[O:33]

Participants

6

Reactant 3

HCID 1118Sulfuric Acid2×HCID 14923Ammonium HydroxideHCID 44545869HCID 44545869, compound

Product 1

HCID 44546064HCID 44546064, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzonitrile (Example 78, prepared according to the method described in US 2008/0319012 A1) (130 mg, 0.31 mmol) in acetic acid (3 mL) was added conc. H2SO4 (0.7 mL) and the mixture was stirred at 100° C. After 2 hours, more conc. H2SO4 (0.2 mL) was added and the mixture was stirred at 100° C. for 1 hour. Then the reaction mixture was cooled to room temperature, diluted with H2O (10 mL) in the ice bath, and neutralized by addition of NH4OH solution to pH 7. The mixture was extracted with CH2Cl2 (3 times) and then the organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by MPLC (MeOH:CH2Cl2=1:20 (v/v) to 1:10 (v/v)) to afford the solid, which was recrystallized from CH2Cl2/MeOH/Et2O to give the title compound (131.6 mg, 68%). 1H NMR (300 MHz, CD3OD) δ 2.53 (3H, s), 4.23 (2H, s), 7.16-7.23 (3H, m), 7.54-7.59 (2H, m), 7.84 (1H, dd), 8.04 (2H, bs), 8.25 (1H, bs), 8.85 (2H, dd). MS (ESI) m/z 439 (MH+).

Workup

  1. stirringthe mixture was stirred at 100° C. for 1 hour
  2. temperatureThen the reaction mixture was cooled to room temperature
  3. extractionThe mixture was extracted with CH2Cl2 (3 times)
  4. dry with materialthe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue was purified by MPLC (MeOH:CH2Cl2=1:20 (v/v) to 1:10 (v/v))
  8. customto afford the solid, which
  9. customwas recrystallized from CH2Cl2/MeOH/Et2O

Sources & evidence

ORD record
ord-54a0e568744e49fbb8d04beb19dfccc0
Source dataset
uspto-grants-2013_04
Patent number
US08410146B2

Reaction notes

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