4-Chloroaniline → HCID 50943107, compound

HRID 1920083Notes

Reaction equation

HRID 1920083 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][CH:11](O)[C:12]([C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=[CH:16][CH:15]=2)=[O:13])=[O:9])=[N:6][CH:7]=1.P(Cl)(Cl)(Cl)(Cl)Cl.[Cl:31][C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][CH:33]=1>C(Cl)(Cl)Cl.C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][CH:11]([NH:36][C:35]2[CH:37]=[CH:38][C:32]([Cl:31])=[CH:33][CH:34]=2)[C:12]([C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=[CH:16][CH:15]=2)=[O:13])=[O:9])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 78124-ChloroanilineHCID 24819Phosphorus pentachlorideHCID 58149557HCID 58149557, compound

Product 1

HCID 50943107HCID 50943107, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

5-bromo-N-(1-hydroxy-2-(naphthalen-1-yl)-2-oxoethyl)picolinamide 113 (0.74 g, 1.93 mmol) in chloroform (20 mL) was reacted with PCl5 (0.43 g, 1.96 mmol). The mixture was heated to 50° C. for 30 minutes and cooled to 0° C. 4-Chloroaniline 114 (0.512 g, 4.01 mmol) in THF (10 mL) was added and allowed to react for 1 hour. The reaction was quenched with water and the product was extracted with ethyl acetate. The organic solution was dried over MgSO4, filtered and concentrated onto silica gel. The product was purified by auto flash column chromatography (30 to 50% CH2Cl2: hexane) followed by titration with diethyl ether to give 5-bromo-N-(1-(4-chlorophenylamino)-2-(naphthalen-1-yl)-2-oxoethyl)picolinamide (Compound-1, 352 mg, 37%). 1H NMR (300 MHz, CDCl3): δ=8.83 (d, J=8.7 Hz, 1H), 8.50 (d, J=1.5 Hz, 1H), 8.46 (d, J=9.6 Hz, 1H), 8.39 (dd, J=1.2, 7.2 Hz, 1H), 8.07-8.03 (m, 2H), 7.93 (dd, J=2.4, 8.7 Hz, 1H), 7.89 (d, J=7.5 Hz, 1H), 7.68-7.63 (m, 1H), 7.56 (t, J=7.8 Hz, 2H), 7.16 (d, J=8.7 Hz, 2H), 7.09-7.03 (m, 1H), 6.82 (d, J=9.0 Hz, 2H) 5.41 (d, J=8.1 Hz, 1H).

Workup

  1. temperaturecooled to 0° C
  2. customto react for 1 hour
  3. customThe reaction was quenched with water
  4. extractionthe product was extracted with ethyl acetate
  5. dry with materialThe organic solution was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated onto silica gel
  8. customThe product was purified by auto flash column chromatography (30 to 50% CH2Cl2: hexane)

Sources & evidence

ORD record
ord-730f164881394cd7869c2ba51c03bab7
Source dataset
uspto-grants-2012_05
Patent number
US08168795B2

Reaction notes

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