3-Fluorobenzoic Acid → HCID 67254555, compound

HRID 1847211Notes

Reaction equation

HRID 1847211 reaction equation
Cl[C:2](OC1C=CC=CC=1)=[O:3].[NH2:11][C:12]1[N:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[CH:13]=1.[F:20][C:21]1[CH:22]=[C:23]([CH:27]2[C:32]3[N:33]=[C:34]4[C:39]([C:31]=3[CH2:30][CH2:29][NH:28]2)=[CH:38][CH:37]=[CH:36][NH:35]4)[CH:24]=[CH:25][CH:26]=1.FC1C=C(C=CC=1)C(O)=O.C(=O)([O-])O.[Na+]>C(N(CC)CC)C.O1CCCC1>[CH3:19][C:14]1[CH:15]=[C:16]([CH3:18])[N:17]=[C:12]([NH:11][C:2]([N:28]2[CH2:29][CH2:30][C:31]3[C:39]4[C:34]([NH:33][C:32]=3[CH:27]2[C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([F:20])[CH:22]=2)=[N:35][CH:36]=[CH:37][CH:38]=4)=[O:3])[CH:13]=1

Participants

8

Reactant 5

HCID 99683-Fluorobenzoic AcidHCID 15891Phenyl chloroformateHCID 215072-Amino-4,6-dimethylpyridineHCID 516892Sodium BicarbonateHCID 178505657HCID 178505657, compound

Product 1

HCID 67254555HCID 67254555, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

To a tetrahydrofuran (1 mL) solution of phenyl chloroformate (157 mg), a tetrahydrofuran (1 mL) solution of 6-amino-2,4-lutidine (122 mg) and triethylamine (0.14 mL) were added under ice cooling, followed by stirring for one hour. The resulting mixture was added to a tetrahydrofuran (0.5 mL) solution of 8-(3-fluorophenyl)-5,6,7,8-tetrahydro-1H-pyrido[4′,3′:4,5]pyrrolo[2,3-b]pyridine (prepared by conducting the operation having the same purpose as that in Example 8→Example 9→Example 10 using 3-fluorobenzoic acid in place of 3-methoxybenzoic acid) (60 mg) and triethylamine (31 μL), followed by stirring at 70° C. for 2 hours. To the reaction mixture, an aqueous saturated sodium hydrogen carbonate solution was added, followed by extraction with ethyl acetate. The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution and saturated saline, dried over anhydrous sodium sulfate and then concentrated. The residue was purified by silica gel column chromatography (parallel separation purification system) and recrystallized from a mixed solvent of ethyl acetate and hexane to obtain the titled compound having the following physical properties (38.7 mg).

Workup

  1. customprepared
  2. stirringby stirring at 70° C. for 2 hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution and saturated saline
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (parallel separation purification system)
  8. customrecrystallized from a mixed solvent of ethyl acetate and hexane

Sources & evidence

ORD record
ord-6c26b8c0250c4257bcb303ffa8977e69
Source dataset
uspto-grants-2015_02
Patent number
US08952158B2

Reaction notes

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