Acetic Acid → 5-(4-dimethylaminobutylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one

HRID 1736211Notes

Reaction equation

HRID 1736211 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]1[C:12]2[C:13](=[O:31])[CH:14]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])=[C:19]([F:30])[CH:18]=3)[O:16][C:11]=2[C:10]([F:32])=[CH:9][C:8]=1[F:33].C=O.[C:36]([BH3-])#[N:37].[Na+].[C:40]([OH:43])(=[O:42])[CH3:41]>CO.C(#N)C.C(OCC)(=O)C>[C:40]([O-:43])(=[O:42])[CH3:41].[NH4+:1].[CH3:40][N:37]([CH3:36])[CH2:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]1[C:12]2[C:13](=[O:31])[CH:14]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])=[C:19]([F:30])[CH:18]=3)[O:16][C:11]=2[C:10]([F:32])=[CH:9][C:8]=1[F:33]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 194348645-(4-aminobutylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one

Product 2

HCID 517165Ammonium AcetateHCID 194348735-(4-dimethylaminobutylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-oneYield 57.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

190 mg (0.412 mmol) of the above 5-(4-aminobutylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one was dissolved in 10 mL of methanol, 0.23 mL (8.2 mmol) of a 37% aqueous solution of formaldehyde, 259 mg (4.12 mmol) of sodium cyanoborohydride and a solution of 0.24 mL (4.1 mmol) of acetic acid in 0.48 mL of methanol were added and the mixture was stirred at room temperature for 24 hours. Ethyl acetate was added to the reaction solution, and the organic layer was separated, washed twice with a 1N aqueous solution of sodium hydroxide and twice with an aqueous saturated solution of sodium chloride, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by high performance liquid chromatography (column: YMC SH-365-15 S-15, acetonitrile: a 0.1M aqueous solution of ammonium acetate=7:3, 40 mL/min.) to give 116 mg of 5-(4-dimethylaminobutylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one (yield: 57%).

Workup

  1. customthe organic layer was separated
  2. washwashed twice with a 1N aqueous solution of sodium hydroxide and twice with an aqueous saturated solution of sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe residue was purified by high performance liquid chromatography (column

Sources & evidence

ORD record
ord-b8f91a013ae249769ab13365c1bbf499
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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