Pyridine → 4-Cyclohexyl-n-{2-[methyl-(1-methyl-piperidin-4-yl)-amino]-benzooxazol-5-yl}-benzamide

HRID 1174936Notes

Reaction equation

HRID 1174936 reaction equation
C(Cl)(=O)C(Cl)=O.[CH:7]1([C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]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>[CH:7]1([C:13]2[CH:14]=[CH:15][C:16]([C:17]([NH:33][C:30]3[CH:31]=[CH:32][C:26]4[O:25][C:24]([N:23]([CH3:22])[CH:34]5[CH2:35][CH2:36][N:37]([CH3:40])[CH2:38][CH2:39]5)=[N:28][C:27]=4[CH:29]=3)=[O:19])=[CH:20][CH:21]=2)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 883374-Cyclohexylbenzoic acidHCID 59558009N2-Methyl-N2-(1-methyl-piperidin-4-yl)-benzooxazole-2,5-diamine

Product 1

HCID 116408854-Cyclohexyl-n-{2-[methyl-(1-methyl-piperidin-4-yl)-amino]-benzooxazol-5-yl}-benzamideYield 62.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Add oxalyl chloride (0.16 mL, 1.82 mmol) and 3 drops of DMF to a stirring suspension of 4-cyclohexyl-benzoic acid (0.197 g, 0.910 mmol) in CH2Cl2 (2.0 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-cyclohexyl-benzoyl chloride solution to a mixture of rac-N2-methyl-N2-(1-methyl-piperidin-4-yl)-benzooxazole-2,5-diamine (0.158 g, 0.607 mmol) and pyridine (0.05 mL) in CH2Cl2 (10 mL). Shake the reaction mixture overnight at room temperature. Wash the mixture with saturated NaHCO3 (aqueous) (2×20 mL), dry the organic phase over Na2SO4, filter, and concentrate the mixture in vacuo. Subject the residue to silica gel flash column chromatography (3×4 g columns, eluting with 5% 2N NH3 in MeOH/CH2Cl2) to yield the desired product as a white solid (0.169 g, 62%). mass spectrum (m/e): 447.3 (M+1). 1H NMR (400 MHz, CDCl3): δ 7.85 (s, 1H), 7.78 (d, J=8.4 Hz, 2H), 7.47 (d, J=2.0 Hz, 1H), 7.35 (dd, J=8.8, 2.0 Hz, 1H), 7.31-7.27 (m, 2H), 7.19 (d, J=8.8 Hz, 1H), 4.19-4.10 (m, 1H), 3.06 (s, 3H), 2.96 (d, J=12.0 Hz, 2H), 2.66-2.50 (m, 1H), 2.31 (s, 3H), 2.15 (dt, J=11.6, 2.4 Hz, 2H), 1.98-1.71 (m, 10H), 1.48-1.33 (m, 3H), 1.31-1.19 (m, 1H).

Workup

  1. concentrationConcentrate the mixture in vacuo
  2. additionadd n-hexane
  3. concentrationre-concentrate
  4. dissolutionre-dissolve in CH2Cl2
  5. additionAdd the resultant 4-cyclohexyl-benzoyl chloride solution
  6. customthe reaction mixture overnight
  7. customat room temperature
  8. washWash the mixture with saturated NaHCO3 (aqueous) (2×20 mL)
  9. dry with materialdry the organic phase over Na2SO4
  10. filtrationfilter
  11. concentrationconcentrate the mixture in vacuo
  12. washto silica gel flash column chromatography (3×4 g columns, eluting with 5% 2N NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-1d44789ffae441839443d61aed97aca9
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

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