Morpholine, hydrochloride (1:1) → 7-[2-(2-Morpholin-4-yl-propyl)-pyridin-4-yl]-imidazo[1,2-a]pyridine

HRID 1446659

Reaction equation

HRID 1446659 reaction equation
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([C:10]3[CH:15]=[CH:14][N:13]=[C:12]([CH2:16][C:17](=O)[CH3:18])[CH:11]=3)=[CH:6][C:5]=12.Cl.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C([BH3-])#N.[Na+]>CO>[N:21]1([CH:17]([CH3:18])[CH2:16][C:12]2[CH:11]=[C:10]([C:7]3[CH:8]=[CH:9][N:4]4[CH:3]=[CH:2][N:1]=[C:5]4[CH:6]=3)[CH:15]=[CH:14][N:13]=2)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 197884Morpholine, hydrochloride (1:1)HCID 5003444Sodium cyanoborohydrideHCID 68544526HCID 68544526, compound

Product 1

HCID 685425037-[2-(2-Morpholin-4-yl-propyl)-pyridin-4-yl]-imidazo[1,2-a]pyridineYield 74%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Dissolve 1-(4-imidazo[1,2-a]pyridin-7-yl-pyridin-2-yl)-propan-2-one (3.9 g, 15.5 mmol) in methanol (400 mL) under nitrogen. Add morpholine hydrochloride (38.4 g, 20 equiv.) followed by 3 {acute over (Å)} Sieves (7.8 g, powdered and dried in a vacuum oven at 100° C. overnight). Stir five minutes then add sodium cyanoborohydride (1.0 M in THF, 28 mL, 1.8 equiv.) via syringe and stir at room temperature for 5 days. Filter to remove insoluble material, washing with methanol. Concentrate to dryness then make basic with 20% NaOH (aq) and extract with ethyl acetate. Wash organics with aqueous saturated sodium chloride then dry over MgSO4. Filter and concentrate then purify by silica gel (Ethyl Acetate→5% Methanol:DCM→10% Methanol:DCM→5% 2M NH3 in methanol:DCM→10% 2 M NH3 in Methanol:DCM) to give product as a tan solid (3.7 g, 74%). MS (ES), m/z 323 (M+1).

Workup

  1. customdried in a vacuum oven at 100° C. overnight)
  2. filtrationFilter
  3. customto remove insoluble material
  4. washwashing with methanol
  5. concentrationConcentrate to dryness
  6. extractionextract with ethyl acetate
  7. dry with materialWash organics with aqueous saturated sodium chloride then dry over MgSO4
  8. filtrationFilter
  9. concentrationconcentrate
  10. customthen purify by silica gel (Ethyl Acetate→5% Methanol:DCM→10% Methanol:DCM→5% 2M NH3 in methanol:DCM→10% 2 M NH3 in Methanol:DCM)

Sources & evidence

ORD record
ord-c517cdeddc1b4dac838390de425b15d6
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Linked notes

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