Acetic Anhydride → HCID 178474546, compound

HRID 1466183Notes

Reaction equation

HRID 1466183 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][C:31]=1[F:32])[CH2:5][NH:6]/[C:7](/[NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[N:23]=1)=[N:8]/[C:9](=[O:20])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1.[C:33](OC(=O)C)(=[O:35])[CH3:34].[NH4+].[Cl-]>N1C=CC=CC=1.CN(C)C1C=CN=CC=1.O.C(OCC)(=O)C>[NH2:8][C:7]([NH2:21])=[NH:6].[Cl:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][C:31]=1[F:32])[CH2:5][N:6](/[C:7](/[NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[N:23]=1)=[N:8]/[C:9](=[O:20])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:17])[F:18])=[CH:12][CH:11]=1)[C:33](=[O:35])[CH3:34]

Participants

9

Reactant 3

HCID 7918Acetic Anhydride2×HCID 25517Ammonium ChlorideHCID 178523898HCID 178523898, compound

Product 2

HCID 3520GuanidineHCID 178474546HCID 178474546, compoundYield 48%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1049PyridineSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Pyridonyl guanidine compound (Z)—N-(((3-chloro-4-fluorobenzyl)amino)((6-hydroxypyridin-2-yl)amino)methylene)-4-(trifluoromethyl)benzamide was prepared based on the procedures described in Example 1. Then, (Z)-N-(((3-chloro-4-fluorobenzyl)amino)((6-hydroxypyridin-2-yl)amino)methylene)-4-(trifluoromethyl)benzamide (0.1 g, 0.214 mmol) was dissolved in pyridine (1 mL) with 4-dimethylaminopyridine (0.026 g, 0.214 mmol) under nitrogen at room temperature and acetic anhydride was added (0.022 g, 0.214 mmol). The reaction mixture was stirred at room temperature for 4 h forming a thick white slurry. Analysis by RP-HPLC indicated a ˜1:1 mixture of starting material and product. Additional pyridine (approximately 0.5 mL) and acetic anhydride (˜10 uL) were added. Stirring was continued for another 4 h then the mixture was diluted with water and ethyl acetate. Saturated aqueous NH4Cl was added to the mixture and the layers were separated. The organic layer was washed with water then brine and dried (MgSO4). Chromatography, eluting with 30-50% ethyl acetate in hexanes, gave a white solid which was triturated with diethyl ether to provide (E)-N—((N-(3-chloro-4-fluorobenzyl)acetamido)((6-hydroxypyridin-2-yl)amino)methylene)-4-(trifluoromethyl)benzamide (52 mg, 48%).

Workup

  1. customforming a thick white slurry
  2. additiona ˜1:1 mixture of starting material and product
  3. stirringStirring
  4. waitwas continued for another 4 h
  5. customthe layers were separated
  6. washThe organic layer was washed with water
  7. dry with materialbrine and dried (MgSO4)
  8. washChromatography, eluting with 30-50% ethyl acetate in hexanes
  9. customgave a white solid which
  10. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-31879826e6ff40a5b86ac75c807dbe97
Source dataset
uspto-grants-2015_04
Patent number
US09000014B2

Reaction notes

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