Pyridine → Rac-n-{2-[methyl-(1-methyl-pyrrolidin-3-ylmethyl)-amino]-benzooxazol-5-yl}-3-(4-trifluoromethyl-phenyl)-acrylamide

HRID 1174939Notes

Reaction equation

HRID 1174939 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]([F:21])([F:20])[C:9]1[CH:14]=[CH:13][C:12]([CH:15]=[CH:16][C:17]([OH:19])=O)=[CH:11][CH:10]=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]([CH2:34][CH:39]1[CH2:35][CH2:36][N:37]([CH3:40])[CH2:38]1)[C:24]1[O:25][C:26]2[CH:32]=[CH:31][C:30]([NH:33][C:17](=[O:19])[CH:16]=[CH:15][C:12]3[CH:11]=[CH:10][C:9]([C:8]([F:7])([F:21])[F:20])=[CH:14][CH:13]=3)=[CH:29][C:27]=2[N:28]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 749403-[4-(Trifluoromethyl)phenyl]prop-2-enoic acidHCID 59558009N2-Methyl-N2-(1-methyl-piperidin-4-yl)-benzooxazole-2,5-diamine

Product 1

HCID 68769638Rac-n-{2-[methyl-(1-methyl-pyrrolidin-3-ylmethyl)-amino]-benzooxazol-5-yl}-3-(4-trifluoromethyl-phenyl)-acrylamideYield 115.3%

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-(4-trifluoromethyl-phenyl)-acrylic acid (0.249 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-(4-trifluoromethyl-phenyl)-acryloyl 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 (0.06 mL) in CH2Cl2 (5.0 mL). Shake the reaction mixture overnight at room temperature. Filter the reaction mixture and wash the product with CH2Cl2. Dry the product on high vacuum to yield the desired product as an off-white solid (0.321 g, 91%). mass spectrum (m/e): 459.0 (M+1), 457.0 (M−1). 1H NMR (400 MHz, CD3OD): δ 8.93-8.89 (m, 1H), 8.71 (dt, J=8.0, 1.8 Hz, 1H), 8.17-8.13 (m, 1H), 7.85-7.72 (m, 4H), 7.55 (d, J=8.8 Hz, 1H), 7.44 (dd, J=8.8, 1.8 Hz, 1H), 6.94 (d, J=15.8 Hz, 1H), 4.57-4.47 (m, 1H), 3.75-3.67 (m, 2H), 3.36-3.29 (m, 2H), 3.28 (s, 3H), 2.96 (s, 3H), 2.41-2.28 (m, 2H), 2.27-2.18 (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-(4-trifluoromethyl-phenyl)-acryloyl chloride solution
  6. customthe reaction mixture overnight
  7. customat room temperature
  8. filtrationFilter the reaction mixture
  9. washwash the product with CH2Cl2
  10. customDry the product on high vacuum

Sources & evidence

ORD record
ord-166d86be597b4d1e91fd62ba239e5fe9
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

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