Pyridine → HCID 11604927, compound

HRID 1174940Notes

Reaction equation

HRID 1174940 reaction equation
C(Cl)(=O)C(Cl)=O.[O:7]([C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17]([OH:19])=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH3:23][N:24]([CH:35]1[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]1)[C:25]1[O:26][C:27]2[CH:33]=[CH:32][C:31]([NH2:34])=[CH:30][C:28]=2[N:29]=1.N1C=CC=CC=1>CN(C=O)C.C(Cl)Cl>[CH3:23][N:24]([CH:35]1[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]1)[C:25]1[O:26][C:27]2[CH:33]=[CH:32][C:31]([NH:34][C:17](=[O:19])[C:16]3[CH:20]=[CH:21][CH:22]=[C:14]([O:7][C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=4)[CH:15]=3)=[CH:30][C:28]=2[N:29]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 195393-Phenoxybenzoic acidHCID 65578Oxalyl chlorideHCID 59558009N2-Methyl-N2-(1-methyl-piperidin-4-yl)-benzooxazole-2,5-diamine

Product 1

HCID 11604927HCID 11604927, compoundYield 46.5%

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 3-phenoxy-benzoic acid (0.247 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 3-phenoxy-benzoyl 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 (5.0 mL). Shake the reaction mixture overnight at room temperature. Wash the mixture with saturated NaHCO3 (aqueous) (3×25 mL), dry the organic phase over Na2SO4, filter, and concentrate the mixture in vacuo. Subject the residue to silica gel flash column chromatography (5×4 g columns, eluting with 5% 2N NH3 in MeOH/CH2Cl2) to yield the desired product as a white solid (0.163 g, 46%). mass spectrum (m/e): 457.0 (M+1), 455.0 (M−1). 1H NMR (400 MHz, CD3OD): δ 7.72-7.67 (m, 2H), 7.60-7.57 (m, 1H), 7.51 (t, J=7.9 Hz, 1H), 7.44-7.38 (m, 2H), 7.35-7.28 (m, 2H), 7.22-7.15 (m, 2H), 7.09-7.05 (m, 2H), 4.18-4.09 (m, 1H), 3.12 (s, 3H), 3.06-3.00 (m, 2H), 2.35 (s, 3H), 2.24 (dt, J=12.4, 2.4 Hz, 2H), 2.03-1.92 (m, 2H), 1.87-1.80 (m, 2H).

Workup

  1. concentrationConcentrate the mixture in vacuo
  2. additionadd n-hexane
  3. concentrationre-concentrate
  4. dissolutionre-dissolve in CH2Cl2
  5. additionAdd the resultant 3-phenoxy-benzoyl chloride solution
  6. customthe reaction mixture overnight
  7. customat room temperature
  8. washWash the mixture with saturated NaHCO3 (aqueous) (3×25 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 (5×4 g columns, eluting with 5% 2N NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-218d0439a8d947dc92602445ba781276
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

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