Chloroacetaldehyde → HCID 89544489, compound

HRID 2203423Notes

Reaction equation

HRID 2203423 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:42]=[C:41]([Cl:43])[CH:40]=[CH:39][C:9]=2[O:10][C:11]2[C:16]([F:17])=[CH:15][C:14]([S:18]([N:21](CC3C=CC(OC)=CC=3OC)[C:22]3[S:26][N:25]=[CH:24][N:23]=3)(=[O:20])=[O:19])=[C:13]([F:38])[CH:12]=2)[CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].Cl[CH2:50][CH:51]=O>C(O)C.O.ClCCl>[Cl:43][C:41]1[CH:40]=[CH:39][C:9]([O:10][C:11]2[C:16]([F:17])=[CH:15][C:14]([S:18]([NH:21][C:22]3[S:26][N:25]=[CH:24][N:23]=3)(=[O:19])=[O:20])=[C:13]([F:38])[CH:12]=2)=[C:8]([C:6]2[N:7]3[CH:50]=[CH:51][N:1]=[C:2]3[CH:3]=[CH:4][CH:5]=2)[CH:42]=1

Participants

7

Reactant 3

HCID 33ChloroacetaldehydeHCID 516892Sodium BicarbonateHCID 89555368HCID 89555368, compound

Product 1

HCID 89544489HCID 89544489, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-(2-(6-aminopyridin-2-yl)-4-chlorophenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (2.43 g, 3.75 mmol) in ethanol (75 mL) and water (9 mL) was added sodium bicarbonate (0.41 g, 4.9 mmol) and chloroacetaldehyde (50% w/w in water, 0.63 mL, 4.9 mmol) at ambient temperature. The mixture was heated at reflux for 16 h, allowed to cool to ambient temperature and diluted with dichloromethane (200 mL) and water (20 mL). The organic layer washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in dichloromethane (50 mL) and trifluoroacetic acid (2 mL) was added. The reaction mixture was stirred for 5 h at ambient temperature and concentrated in vacuo. The residue was purified by column chromatography eluting with a 0-10% gradient of methanol in ethyl acetate to afford 4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a pale yellow solid in 43% yield (0.84 g): 1H NMR (300 MHz, DMSO-d6) δ8.14 (s, 1H), 7.93 (d, J=1.5 Hz, 2H), 7.87-7.78 (m, 2H), 7.76-7.66 (m, 2H), 7.62-7.52 (m, 1H), 7.42-7.30 (m, 3H); MS (ES+) m/z 519.8 (M+1), 521.8 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 16 h
  3. washThe organic layer washed with brine (50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in dichloromethane (50 mL)
  8. additiontrifluoroacetic acid (2 mL) was added
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography
  11. washeluting with a 0-10% gradient of methanol in ethyl acetate

Sources & evidence

ORD record
ord-d4810292e7d24a5a86dc4ea1812a4152
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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