Tetrahydrofuran → 7-[6-(2-Morpholin-4-yl-propyl)-pyridin-2-yl]-imidazo[1,2-a]pyridine

HRID 1446711Notes

Reaction equation

HRID 1446711 reaction equation
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([C:10]3[N:15]=[C:14]([CH2:16][C:17](=O)[CH3:18])[CH:13]=[CH:12][CH:11]=3)=[CH:6][C:5]=12.Cl.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.[BH3-]C#N.[Na+].C1COCC1>CO>[N:21]1([CH:17]([CH3:18])[CH2:16][C:14]2[N:15]=[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:11]=[CH:12][CH:13]=2)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 197884Morpholine, hydrochloride (1:1)HCID 5003444Sodium cyanoborohydrideHCID 68541679HCID 68541679, compound

Product 1

HCID 685428437-[6-(2-Morpholin-4-yl-propyl)-pyridin-2-yl]-imidazo[1,2-a]pyridineYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a well mixed round bottomed flask under N2 charge 1-(6-Imidazo[1,2-a]pyridin-7-yl-pyridin-2-yl)-propan-2-one (1.8 g, 7.2 mmol), morpholine mono HCl salt (16 g, 129 mmol), 3 Å molecular sieves (powdered, vacuum oven dried 110° C. for 24 hours., 3.6 g), methanol (200 mL), and 1 M NaCNBH3 solution in THF (12.9 mL, 12.9 mmol). Stir for 24 hours. at room temp. Filter through Celite® strip off solvents under reduced pressure. Take up into DCM and adjust pH to 10 with 5N NaOH and extract with DCM (5×). Concentrate DCM under reduced pressure and chromatograph on (120 g ISCO®) SiO2 eluting with a slow gradient of 0% to 10% 2 M NH3 in MeOH with the balance DCM. Strip off solvents under reduced pressure to give clear oil 1.67 g (72%) MS(ES), m/z 323 (M+1).

Workup

  1. additionIn a well mixed round bottomed flask under N2 charge
  2. customat room temp
  3. filtrationFilter through Celite® strip off solvents under reduced pressure
  4. extractionextract with DCM (5×)

Sources & evidence

ORD record
ord-3ae76be71c44420a84dd469c35ebe81f
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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