Sodium hydride → 3-(4-Fluorophenyl)-1-[2-(morpholin-4-yl)ethoxy]-2-(pyridin-4-yl)-1h-pyrrolo[3,2-b]pyridine

HRID 429195Notes

Reaction equation

HRID 429195 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[N:10]([OH:17])[C:9]=2[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.Cl.Cl[CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.[H-].[Na+]>CN(C)C=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[N:10]([O:17][CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:9]=2[C:18]2[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 52882383-(4-Fluorophenyl)-1-Hydroxy-2-(Pyridin-4-Yl)-1h-Pyrrolo(3,2-B)Pyridine

Product 1

HCID 129684973-(4-Fluorophenyl)-1-[2-(morpholin-4-yl)ethoxy]-2-(pyridin-4-yl)-1h-pyrrolo[3,2-b]pyridineYield 66.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(4-fluorophenyl)-1-hydroxy-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b]pyridine (0.20 g, 0.65 mmol) and 2-chloroethylmorpholine hydrochloride (0.24 g, 6.56 mmol) in dimethylformamide (5 ml) was added sodium hydride (100 mg, 60% in oil). The reaction mixture was stiffed overnight and quenched with 10% HCl (2 ml). The pH was adjusted to pH=8-9 by the addition of saturated sodium bicarbonate solution and the product was extracted into ethyl acetate. The combined extracts were dried over anhydrous MgSO4 and concentrated in vacuo to give an oil. Purified by flash column chromatography (50%-80% ethyl acetate/hexanes, followed by 95/5% methylene chloride/methanol gradient) gave 3-(4-fluorophenyl)-1-[2-(morpholin-4-yl)ethoxy]-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b]pyridine (180 mg) which recrystallized from hexanes/ethyl acetate to give a white solid.

Workup

  1. customquenched with 10% HCl (2 ml)
  2. additionThe pH was adjusted to pH=8-9 by the addition of saturated sodium bicarbonate solution
  3. extractionthe product was extracted into ethyl acetate
  4. dry with materialThe combined extracts were dried over anhydrous MgSO4
  5. concentrationconcentrated in vacuo
  6. customto give an oil
  7. customPurified by flash column chromatography (50%-80% ethyl acetate/hexanes, followed by 95/5% methylene chloride/methanol gradient)

Sources & evidence

ORD record
ord-5a99c39a869a4f44aa67cc18ead5ddf6
Source dataset
uspto-grants-2001_11
Patent number
US06316464B1

Reaction notes

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