3,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}-N-(2-hydroxyethoxy)benzamide → 3,4-Difluoro-2-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)benzamide

HRID 1793016Notes

Reaction equation

HRID 1793016 reaction equation
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH2:25][O:26]C3CCCCO3)=[CH:19][C:18]=2[F:33])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]>CCO.Cl.O>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH2:25][OH:26])=[CH:19][C:18]=2[F:33])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

Participants

5

Reactant 1

HCID 220256673,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}-N-(2-hydroxyethoxy)benzamide

Product 1

HCID 101726823,4-Difluoro-2-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)benzamideYield 100%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

3,4-Difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}-N-(2-hydroxyethoxy)benzamide (115 mg, 0.25 mmol) was dissolved in EtOH (4 mL) to which was added 1 M HCl (5 drops). This reaction mixture was stirred overnight at RT, then the mixture was diluted with water (50 mL) and extracted with EtOAc (4×30 mL). The combined EtOAc fractions were washed with water (2×20 mL), brine (50 mL) and dried (Na2SO4) then the solvent removed under reduced pressure to afford a white solid which was purified by filtration through a plug of silica gel (EtOAc as eluant) to afford 3,4-difluoro-2-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)benzamide as a cream solid (94 mg, 100%); m.p. (Et2O/hexane) 169–172° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.84 (br s, 1 H), 8.91 (br s, 1 H), 7.46–7.40 (m, 1 H), 7.29–7.19 (m, 2 H), 7.10 (dd, J=8.3, 1.6 Hz, 1 H), 6.78 (ddd, J=8.9, 8.9, 4.8 Hz, 1 H), 5.29 (t, J=5.9 Hz, 1 H), 4.76 (br s, 1 H), 4.27 (d, J=5.9 Hz, 2 H), 3.84 (t, J=4.8 Hz, 2 H), 3.56 (t, J=4.8 Hz, 2 H). Anal. calcd. for C18H15F3N2O4: C, 56.9; H, 4.0; N, 7.4. Found C, 56.8; H, 4.0; N, 7.4.

Workup

  1. extractionextracted with EtOAc (4×30 mL)
  2. washThe combined EtOAc fractions were washed with water (2×20 mL), brine (50 mL)
  3. dry with materialdried (Na2SO4)
  4. customthe solvent removed under reduced pressure
  5. customto afford a white solid which
  6. filtrationwas purified by filtration through a plug of silica gel (EtOAc as eluant)

Sources & evidence

ORD record
ord-443998a5f675458886606cde78f87851
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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