Pyridine → HCID 11690740, compound

HRID 1174941Notes

Reaction equation

HRID 1174941 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:12]=[CH:11][C:10]([C:13]([OH:15])=O)=[CH:9][CH:8]=1.[CH3:22][N:23]([CH:34]1[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]1)[C:24]1[O:25][C:26]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][C:27]=2[N:28]=1.N1C=CC=CC=1>CN(C=O)C.C(Cl)Cl>[CH3:22][N:23]([CH:34]1[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]1)[C:24]1[O:25][C:26]2[CH:32]=[CH:31][C:30]([NH:33][C:13]([C:10]3[CH:9]=[CH:8][C:7]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:12][CH:11]=3)=[O:15])=[CH:29][C:27]=2[N:28]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 66724(1,1'-Biphenyl)-4-carboxylic acidHCID 59558009N2-Methyl-N2-(1-methyl-piperidin-4-yl)-benzooxazole-2,5-diamine

Product 1

HCID 11690740HCID 11690740, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Add oxalyl chloride (0.20 mL, 2.30 mmol) and 3 drops of DMF to a stirring suspension of Biphenyl-4-carboxylic acid (0.240 g, 1.15 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 biphenyl-4-carbonyl chloride solution to a mixture of rac-N2-methyl-N2-(1-methyl-piperidin-4-yl)-benzooxazole-2,5-diamine (0.200 g, 0.768 mmol) and pyridine (0.06 mL) in CH2Cl2 (10 mL). Shake the reaction mixture overnight at room temperature. Wash the mixture with saturated NaHCO3 (aqueous) (2×25 mL), dry the organic phase over Na2SO4, filter, and concentrate the mixture in vacuo. Subject the residue to silica gel 130 flash column chromatography (5×4 g columns, eluting with 5% 2N NH3 in MeOH/CH2Cl2) to yield the desired product (0.168 g, 50%). mass spectrum (m/e): 441.3 (M+1). 1H NMR (400 MHz, CD3OD): δ 8.01-7.97 (m, 2H), 7.74-7.70 (m, 3H), 7.67-7.64 (m, 2H), 7.48-7.42 (m, 2H), 7.39-7.31 (m, 2H), 7.26 (d, J=8.4 Hz, 1H), 4.12-4.02 (m, 1H), 3.06 (s, 3H), 2.97 (d, J=12.0 Hz, 2H), 2.30 (s, 3H), 2.17 (dt, J=12.4, 2.8 Hz, 2H), 1.91 (dq, J=12.0, 4.0 Hz, 2H), 1.76 (d, J=12.6 Hz, 2H).

Workup

  1. concentrationConcentrate the mixture in vacuo
  2. additionadd n-hexane
  3. concentrationre-concentrate
  4. dissolutionre-dissolve in CH2Cl2
  5. additionAdd the resultant biphenyl-4-carbonyl chloride solution
  6. customthe reaction mixture overnight
  7. customat room temperature
  8. washWash the mixture with saturated NaHCO3 (aqueous) (2×25 mL)
  9. dry with materialdry the organic phase over Na2SO4
  10. filtrationfilter
  11. concentrationconcentrate the mixture in vacuo
  12. washto silica gel 130 flash column chromatography (5×4 g columns, eluting with 5% 2N NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-0467bfaa3cf646b99d98bf4a8a1c863f
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

Loading…