3-Phenoxybenzoic acid → n-{2-[Methyl-(1-methyl-pyrrolidin-3-ylmethyl)-amino]-benzooxazol-5-yl}-3-phenoxy-benzamide

HRID 1174930Notes

Reaction equation

HRID 1174930 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.[O:20]([C:27]1[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=1)[C:30](O)=[O:31])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=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])[C:29]3[CH:33]=[CH:34][CH:35]=[C:27]([O:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH:28]=3)=[CH:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 195393-Phenoxybenzoic 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 57771779n-{2-[Methyl-(1-methyl-pyrrolidin-3-ylmethyl)-amino]-benzooxazol-5-yl}-3-phenoxy-benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Combine rac-N2-methyl-N2-(1-methyl-pyrrolidin-3-ylmethyl)-benzooxazole-2,5-diamine (0.034 g, 0.131 mmol), 3-phenoxy-benzoic acid (0.042 g, 0.196 mmol), HATU (0.050 g, 0.131 mmol), polystyrene-bound diisopropylamine (0.327 g, loading: 2.0 to 3.5 mmol/g), and CH2Cl2 (10 mL). Shake the mixture overnight at room temperature. Filter the mixture and wash the polystyrene resin with 1:1 CH2Cl2/MeOH. Concentrate the solution to yield a yellow residue. Dilute with CH2Cl2 and wash with 1.0M NaOH (2×25 mL), dry over Na2SO4, filter, and concentrate in vacuo after adsorption onto silica gel. Subject the mixture to flash column chromatography on an ISCO Companion (4 g column, 10% 2M NH3 in MeOH/CH2Cl2) to yield the desired compound as a white oil. Dilute with CH2Cl2 and n-hexane and concentrate in vacuo. Pump for 2 h to yield the desired compound as a white solid (0.027 g, 45%). mass spectrum (m/e): 457.3 (M+1), 455.3 (M−1). 1H NMR (400 MHz, CDCl3): δ 7.84 (s, 1H), 7.56 (d, J=7.6 Hz, 1H), 7.51-7.45 (m, 2H), 7.41 (t, J=8.0 Hz, 1H), 7.37-7.29 (m, 3H), 7.20-7.10 (m, 3H), 7.04-7.00 (m, 2H), 3.59-3.48 (m, 2H), 3.18 (s, 3H), 2.74-2.50 (m, 4H), 2.38-2.33 (m, 1H), 2.35 (s, 3H), 2.05-1.95 (m, 1H), 1.59-1.49 (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. concentrationConcentrate the solution
  6. customto yield a yellow residue
  7. washwash with 1.0M NaOH (2×25 mL)
  8. dry with materialdry over Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate in vacuo after adsorption onto silica gel

Sources & evidence

ORD record
ord-27684374678549cca4c0d682de37f1f2
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

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