Hydrochloric Acid → HCID 10150921, compound

HRID 1793025Notes

Reaction equation

HRID 1793025 reaction equation
[F:1][C:2]1[C:3]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][CH2:27]I)=[CH:21][C:20]=2[F:29])=[C:4]([CH:14]=[CH:15][C:16]=1[F:17])[C:5]([NH:7][O:8][CH2:9][CH2:10][O:11]C=C)=[O:6].[CH3:30][NH:31][CH3:32].Cl.C([O-])([O-])=O.[K+].[K+].[Na+].[Cl-]>CC(N(C)C)=O.O.CCO>[CH3:30][N:31]([CH3:32])[CH2:27][CH2:26][CH2:25][C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:3]2[C:2]([F:1])=[C:16]([F:17])[CH:15]=[CH:14][C:4]=2[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6])=[C:20]([F:29])[CH:21]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 5234Sodium ChlorideHCID 11430Potassium CarbonateHCID 22025689HCID 22025689, compound

Product 1

HCID 10150921HCID 10150921, compoundYield 36%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

3,4-Difluoro-2-[2-fluoro-4-(3-iodopropyl)anilino]-N-[2-(vinyloxy)ethoxy]benzamide (200 mg, 0.39 mmol) was dissolved in DMA (10 mL), to which was added dimethylamine (0.15 mL of a 40% solution in water). This mixture was stirred at RT for 15 hours, then the DMA removed under reduced pressure, affording a yellow oil. This oil was then dissolved in EtOH (6 mL), to which was added 1 M HCl solution (4 mL). The resulting mixture was stirred at RT for 15 h. The reaction mixture was then diluted with water (50 mL) and this aqueous solution basicified with solid K2CO3 and saturated with solid NaCl. The resulting solution was extracted with EtOAc (3×50 mL), the combined organic extract dried (Na2SO4) and the solvent removed under reduced pressure to afford an oil. This oil was purified by column chromatography on silica gel (1% NH4OH in 25% MeOH/CH2Cl2 as eluant) to give 2-{4-[3-(dimethylamino)propyl]-2-fluoroanilino}-3,4-difluoro-N-(2-hydroxyethoxy)benzamide as a cream foam (55 mg, 36%). 1H NMR [400 MHz, (CD3)2SO] δ 11.70 (v br s, 1 H), 8.82 (br s, 1 H), 7.44–7.38 (m, 1 H), 7.14–7.06 (m, 1H), 7.05 (dd, J=12.5, 1.6 Hz, 1 H), 6.89 (dd, J=8.2, 1.6 Hz, 1 H), 6.82 (ddd, J=8.7, 8.7, 4.5 Hz, 1 H), 4.53 (br s, 1 H), 3.85 (t, J=4.9 Hz, 2 H), 3.57 (t, J=4.9 Hz, 2 H), 2.53 (t, J=7.5 Hz, 2 H), 2.24 (t, J=7.1 Hz, 2 H), 2.16 (s, 6 H), 1.67 (q, J=7.5 Hz, 2H). Anal. calcd. for C20H24F3N3O3.0.75H2O: C, 56.5; H, 6.1; N, 9.9. Found C, 56.4; H, 6.4; N, 9.1.

Workup

  1. customthe DMA removed under reduced pressure
  2. customaffording a yellow oil
  3. stirringThe resulting mixture was stirred at RT for 15 h
  4. extractionThe resulting solution was extracted with EtOAc (3×50 mL)
  5. extractionthe combined organic extract
  6. dry with materialdried (Na2SO4)
  7. customthe solvent removed under reduced pressure
  8. customto afford an oil
  9. customThis oil was purified by column chromatography on silica gel (1% NH4OH in 25% MeOH/CH2Cl2 as eluant)

Sources & evidence

ORD record
ord-a17282e9a7c047d2bd19b7693a12a426
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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