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

HRID 1174927Notes

Reaction equation

HRID 1174927 reaction equation
[CH3:1][N:2]([CH2:13][CH:14]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15]1)[C:3]1[O:4][C:5]2[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][C:6]=2[N:7]=1.[F:20][C:21]([F:34])([F:33])[C:22]1[CH:27]=[CH:26][C:25]([CH:28]=[CH:29][C:30](O)=[O:31])=[CH:24][CH:23]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH3:1][N:2]([CH2:13][CH:14]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15]1)[C:3]1[O:4][C:5]2[CH:11]=[CH:10][C:9]([NH:12][C:30](=[O:31])[CH:29]=[CH:28][C:25]3[CH:24]=[CH:23][C:22]([C:21]([F:33])([F:34])[F:20])=[CH:27][CH:26]=3)=[CH:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 749403-[4-(Trifluoromethyl)phenyl]prop-2-enoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57771749Rac-n2-methyl-n2-(1-methyl-pyrrolidin-3-ylmethyl)-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 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Combine rac-N2-methyl-N2-(1-methyl-pyrrolidin-3-ylmethyl)-benzooxazole-2,5-diamine (0.040 g, 0.154 mmol), 3-(4-trifluoromethyl-phenyl)-acrylic acid (0.050 g, 0.230 mmol), HATU (0.058 g, 0.154 mmol), polystyrene-bound diisopropylamine (0.385 g, loading: 2.0 to 3.5 mmol/g), and CH2Cl2 (20 mL). Shake the mixture overnight at room temperature. Filter the mixture and wash the polystyrene resin with 1:1 CH2Cl2/MeOH. Subject the mixture to flash column chromatography (12 g column, eluting with 10% 2M NH3 in MeOH/CH2Cl2) to yield the product as a yellow-white solid (0.040 g, 57%). mass spectrum (m/e): 459.0 (M+1), 457.0 (M−1). 1H NMR (400 MHz, CDCl3): δ 7.75 (d, J=15.2 Hz, 1H), 7.61 (m, 4H), 7.53 (d, J=12.4 Hz, 2H), 7.37 (d, J=8.0 Hz, 1H), 7.20 (d, J=8.0 Hz, 1H), 6.64 (d, J=15.6 Hz, 1H), 3.62-3.49 (m, 2H), 3.20 (s, 3H), 2.77-2.55 (m, 4H), 2.44-2.37 (m, 1H), 2.38 (s, 3H), 2.09-1.98 (m, 1H), 1.63-1.53 (m, 1H).

Workup

  1. customthe mixture overnight
  2. customat room temperature
  3. filtrationFilter the mixture
  4. washwash the polystyrene resin with 1:1 CH2Cl2/MeOH
  5. washto flash column chromatography (12 g column, eluting with 10% 2M NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-acc382a5cfb54b9e83d1792cb9a7f495
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

Loading…