4-Fluorobenzoic Acid → HCID 20134105, compound

HRID 580522Notes

Reaction equation

HRID 580522 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.[S:11](Cl)(Cl)=O.[NH2:15][C:16]1[C:24]2N=C[CH:21]=[CH:20][C:19]=2S[C:17]=1[NH2:25].CN(C)P([N:33]([CH3:35])[CH3:34])(N(C)C)=O>C(#N)C.C(=O)(O)[O-].[Na+]>[NH2:15][C:16]1[C:17]([NH:25][C:6](=[O:8])[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:10][CH:9]=2)=[CH:34][N:33]=[C:35]2[S:11][C:20]([CH3:21])=[CH:19][C:24]=12

Participants

7

Reactant 4

HCID 99734-Fluorobenzoic AcidHCID 12679HexamethylphosphoramideHCID 24386Thionyl ChlorideHCID 67938339HCID 67938339, compound

Product 1

HCID 20134105HCID 20134105, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 308 mg of 4-fluorobenzoic acid in 5 ml of anhydrous hexamethylphosphoramide and 0.5 ml of anhydrous acetonitrile is added dropwise 250 mg of thionyl chloride at -5°-0° C. under nitrogen. After stirring at the same temperature for 30 minutes, 358 mg of diaminothienopyridine D1 is added and stirred at O°-5° C. for 3 hours. The mixture is diluted with ice-water and neutralized with saturated aqueous sodium bicarbonate. The resulting crystals are filtered, washed with water and dried to yield 630 mg of 4-amino-2-methyl-5-(4-fluorobenzoylamino)thieno[2,3-b]pyridine E1. It is suspended in 15 ml of polyphosphoric acid and heated at 140° C. with stirring under nitrogen. The cooled mixture is poured into ice-water and neutralized with aqueous sodium hydroxide. The product is extracted with ethyl acetate and the extract is washed with water, dried and evaporated. The residue is chromatographed on silica gel with chloroform-methanol (25:1 v/v) as eluent to afford 457 mg (81%) of F1 as colorless crystals.

Workup

  1. stirringstirred at O°-5° C. for 3 hours
  2. filtrationThe resulting crystals are filtered
  3. washwashed with water
  4. customdried

Sources & evidence

ORD record
ord-d3a8b4da8cc243d683ed70ff82078f24
Source dataset
uspto-grants-1988_06
Patent number
US04753951

Reaction notes

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