Pyridine → HCID 57771747, compound

HRID 1174945Notes

Reaction equation

HRID 1174945 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:22])=O)=[CH:16][CH:15]=2)=[CH:10][CH:9]=1.[NH2:23][C:24]1[CH:41]=[CH:40][C:27]2[N:28]=[C:29]([N:31]([CH3:39])[CH2:32][CH2:33][N:34]([CH3:38])[C:35](=[O:37])[CH3:36])[S:30][C:26]=2[CH:25]=1.N1C=CC=CC=1>CN(C=O)C.C(Cl)Cl>[C:35]([N:34]([CH3:38])[CH2:33][CH2:32][N:31]([CH3:39])[C:29]1[S:30][C:26]2[CH:25]=[C:24]([NH:23][C:20]([C:17]3[CH:16]=[CH:15][C:14]([C:11]4[CH:10]=[CH:9][C:8]([F:7])=[CH:13][CH:12]=4)=[CH:19][CH:18]=3)=[O:22])[CH:41]=[CH:40][C:27]=2[N:28]=1)(=[O:37])[CH3:36]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 27826894-(4-Fluorophenyl)benzoic acidHCID 57771701HCID 57771701, compound

Product 1

HCID 57771747HCID 57771747, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Add oxalyl chloride (0.20 mL, 2.30 mmol) and 4 drops of DMF to a stirring suspension of 4′-fluoro-biphenyl-4-carboxylic acid (0.243 g, 1.13 mmol) in CH2Cl2 (5.0 mL). Stir the reaction mixture at room temperature for 2 h. Concentrate the mixture in vacuo, add n-hexane, re-concentrate, and re-dissolve in CH2Cl2. Add the resultant 4′-fluoro-biphenyl-4-carbonyl chloride solution to a mixture of rac-N-{2-[(6-amino-benzothiazol-2-yl)-methyl-amino]-ethyl}-N-methyl-acetamide (0.146 g, 0.524 mmol) and pyridine (0.06 mL) in CH2Cl2 (10 mL). Shake the reaction mixture overnight at room temperature. Subject the residue to silica gel flash column chromatography (3×4 g columns, eluting with 5-10% ethyl acetate/n-hexane to remove impurities, then flushing off product with 2N NH3/MeOH). Triturate the residue with CH2Cl2 to yield the desired product as a white solid (0.110 g, 44%). mass spectrum (m/e): 477.0 (M+1).

Workup

  1. concentrationConcentrate the mixture in vacuo
  2. additionadd n-hexane
  3. concentrationre-concentrate
  4. dissolutionre-dissolve in CH2Cl2
  5. additionAdd the resultant 4′-fluoro-biphenyl-4-carbonyl chloride solution
  6. customthe reaction mixture overnight
  7. customat room temperature
  8. washeluting with 5-10% ethyl acetate/n-hexane
  9. customto remove impurities
  10. customflushing off product with 2N NH3/MeOH)
  11. customTriturate the residue with CH2Cl2

Sources & evidence

ORD record
ord-050da7f8803f4e1da0cb208c1404a38e
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

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