Hydrochloric Acid → 5-(4-morpholinyl)-3-(1-naphthalenylmethyl)-3,4-dihydro-7H-imidazo[4,5-b]pyridin-7-one

HRID 1399782Notes

Reaction equation

HRID 1399782 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH2:11][C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=[CH:14][CH:13]=3)[CH:9]=[N:10][C:5]2=[C:4]([O:22]C)[CH:3]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.Cl>O>[N:24]1([C:2]2[NH:7][C:6]3[N:8]([CH2:11][C:12]4[C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[CH:15]=[CH:14][CH:13]=4)[CH:9]=[N:10][C:5]=3[C:4](=[O:22])[CH:3]=2)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 896479945-chloro-7-(methyloxy)-3-(1-naphthalenylmethyl)-3H-imidazo[4,5-b]pyridine

Product 1

HCID 716125525-(4-morpholinyl)-3-(1-naphthalenylmethyl)-3,4-dihydro-7H-imidazo[4,5-b]pyridin-7-oneYield 28.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 5-chloro-7-(methyloxy)-3-(1-naphthalenylmethyl)-3H-imidazo[4,5-b]pyridine (140 mg, 0.432 mmol) and morpholine (2.5 mL, 28.7 mmol) was irradiated in a microwave oven for 4 h at 200° C. The mixture was diluted with water and the pH was adjusted to ca. 7 by the addition of 1 N HCl. The precipitate formed was collected, washed with water and air dried. It was then dissolved in DMSO and purified by RP-HPLC (Gilson, 25-80% AcCN in water plus 0.1% TFA). The fractions containing product were collected, neutralized by the addition of aqueous NaHCO3 sat sol and the volume was reduced to ½-⅓ of the original. The precipitate was collected by filtration, washed with water and dried overnight in a vacuum oven at 45° C. to give 5-(4-morpholinyl)-3-(1-naphthalenylmethyl)-3,4-dihydro-7H-imidazo[4,5-b]pyridin-7-one (45 mg, 0.122 mmol, 28.3% yield). MS (ES+) m/e 361 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.83 (br. s., 1H), 8.32-8.47 (m, 1H), 8.00 (s, 1H), 7.94-7.98 (m, 1H), 7.89 (d, J=8.08 Hz, 1H), 7.52-7.61 (m, 2H), 7.47 (dd, J=8.08, 7.07 Hz, 1H), 7.35 (d, J=6.32 Hz, 1H), 6.07 (s, 1H), 5.77 (s, 2H), 3.65-3.75 (m, 4H), 3.35-3.43 (m, 4H)

Workup

  1. customwas irradiated in a microwave oven for 4 h at 200° C
  2. customThe precipitate formed
  3. customwas collected
  4. washwashed with water and air
  5. customdried
  6. dissolutionIt was then dissolved in DMSO
  7. custompurified by RP-HPLC (Gilson, 25-80% AcCN in water plus 0.1% TFA)
  8. additionThe fractions containing product
  9. customwere collected
  10. additionneutralized by the addition of aqueous NaHCO3
  11. filtrationThe precipitate was collected by filtration
  12. washwashed with water
  13. customdried overnight in a vacuum oven at 45° C.

Sources & evidence

ORD record
ord-3307a0e2c7b64d29bdb27c390d884e16
Source dataset
uspto-grants-2014_12
Patent number
US08906910B2

Reaction notes

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