Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → Rac-6-(4-fluoro-phenyl)-n-{2-[methyl-(1-methyl-pyrrolidin-3-ylmethyl)-amino]-benzooxazol-5-yl}-nicotinamide

HRID 1174932Notes

Reaction equation

HRID 1174932 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]1[CH:26]=[CH:25][C:24]([C:27]2[CH:35]=[CH:34][C:30]([C:31](O)=[O:32])=[CH:29][N:28]=2)=[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>[F:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[CH:35]=[CH:34][C:30]([C:31]([NH:12][C:9]3[CH:10]=[CH:11][C:5]4[O:4][C:3]([N:2]([CH3:1])[CH2:13][CH:14]5[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15]5)=[N:7][C:6]=4[CH:8]=3)=[O:32])=[CH:29][N:28]=2)=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 227301866-(4-Fluorophenyl)nicotinic acidHCID 57771749Rac-n2-methyl-n2-(1-methyl-pyrrolidin-3-ylmethyl)-benzooxazole-2,5-diamine

Product 1

HCID 11684003Rac-6-(4-fluoro-phenyl)-n-{2-[methyl-(1-methyl-pyrrolidin-3-ylmethyl)-amino]-benzooxazol-5-yl}-nicotinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Combine rac-N2-Methyl-N2-(1-methyl-pyrrolidin-3-ylmethyl)-benzooxazole-2,5-diamine (0.034 g, 0.131 mmol), 6-(4-fluoro-phenyl)-nicotinic acid (0.043 g, 0.198 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 in vacuo. Dilute with CH2Cl2, wash with 1.0M NaOH (2×25 mL), dry over Na2SO4, filter, and concentrate in vacuo. Subject the residue to silica gel flash column chromatography (4 g column, eluting with 10% 2N NH3 in MeOH/CH2Cl2) to yield the desired product as an impure mixture. Re-subject the mixture to silica gel flash column chromatography (3×4 g columns, 5% 2N NH3 in MeOH/CH2Cl2) to yield the desired product as a white oil (0.030 g, 51%). mass spectrum (m/e): 460.0 (M+1), 458.0 (M−1). 1H NMR (400 MHz, CDCl3): δ 9.10 (s, 1H), 8.31 (s, 1H), 8.22 (dd, J=8.0, 2.4 Hz, 1H), 8.03-7.97 (m, 2H), 7.72 (d, J=8.4 Hz, 1H), 7.53 (s, 1H), 7.34 (d, J=8.4 Hz, 1H), 7.20-7.11 (m, 3H), 3.58-3.46 (m, 2H), 3.16 (s, 3H), 2.72-2.56 (m, 3H), 2.55-2.48 (m, 1H), 2.38-2.32 (m, 1H), 2.33 (s, 3H), 2.04-1.95 (m, 1H), 1.57-1.48 (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 in vacuo
  6. additionDilute with CH2Cl2
  7. washwash with 1.0M NaOH (2×25 mL)
  8. dry with materialdry over Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. washto silica gel flash column chromatography (4 g column, eluting with 10% 2N NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-7c723565710644869e43efb7ba1f5fa0
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

Loading…