Sodium Bicarbonate → 4-(1-(2,4-Dimethyl-5-(6-morpholino-3H-imidazo[4,5-c]pyridin-2-yl)benzoyl)azetidin-3-yl)benzonitrile

HRID 1488002Notes

Reaction equation

HRID 1488002 reaction equation
[CH:1]([C:3]1[C:4]([CH3:24])=[CH:5][C:6]([CH3:23])=[C:7]([CH:22]=1)[C:8]([N:10]1[CH2:13][CH:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)[CH2:11]1)=[O:9])=O.[O:25]1[CH2:30][CH2:29][N:28]([C:31]2[N:36]=[CH:35][C:34]([NH2:37])=[C:33]([NH2:38])[CH:32]=2)[CH2:27][CH2:26]1.C(=O)(O)[O-].[Na+]>C(O)C>[CH3:23][C:6]1[CH:5]=[C:4]([CH3:24])[C:3]([C:1]2[NH:37][C:34]3[CH:35]=[N:36][C:31]([N:28]4[CH2:29][CH2:30][O:25][CH2:26][CH2:27]4)=[CH:32][C:33]=3[N:38]=2)=[CH:22][C:7]=1[C:8]([N:10]1[CH2:11][CH:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)[CH2:13]1)=[O:9]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 900211616-(Morpholin-4-yl)pyridine-3,4-diamine2×HCID 900213214-(1-(5-Formyl-2,4-dimethylbenzoyl)azetidin-3-yl)benzonitrile2×

Product 1

HCID 900330084-(1-(2,4-Dimethyl-5-(6-morpholino-3H-imidazo[4,5-c]pyridin-2-yl)benzoyl)azetidin-3-yl)benzonitrileYield 38.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

Into a 50-mL round-bottom flask, was placed a solution of 4-(1-(5-formyl-2,4-dimethylbenzoyl)azetidin-3-yl)benzonitrile (compound 151.4, 159 mg, 0.50 mmol) in ethanol (16 mL). 6-Morpholinopyridine-3,4-diamine (compound 151.2, 194 mg, 1.00 mmol) and NH4OAc (308 mg, 4.00 mmol) were added to the reaction. The reaction mixture was stirred for 3 days at 70° C. under air. The pH of the solution was adjusted to 8-9 with sodium bicarbonate (sat.). The reaction mixture was extracted with 1×100 mL of ethyl acetate. The organic layer was washed with 3×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product (200 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-010(Waters)): Column, SunFire Prep C18 OBD Column, 5 μm, 19*150 mm; mobile phase, WATER WITH 0.05% TFA and CH3CN (20.0% CH3CN up to 36.0% in 10 min, up to 100.0% in 1 min, down to 20.0% in 2 min); Detector, UV 254 and 220 nm. This resulted in 94.1 mg (38%) of the title compound as a brown solid. m/z (ES+) 493 (M+H)+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. extractionThe reaction mixture was extracted with 1×100 mL of ethyl acetate
  3. washThe organic layer was washed with 3×50 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product (200 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-010(Waters))
  7. waitmobile phase, WATER WITH 0.05% TFA and CH3CN (20.0% CH3CN up to 36.0% in 10 min
  8. waitup to 100.0% in 1 min
  9. waitdown to 20.0% in 2 min)

Sources & evidence

ORD record
ord-6c6b13a93adf4e9f929d653d77ab2e48
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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