Bromoacetonitrile → 2-((5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methoxy)acetonitrile

HRID 931561Notes

Reaction equation

HRID 931561 reaction equation
[NH2:1][C:2]1([CH2:19][OH:20])[C:15]2[C:10](=[N:11][CH:12]=[C:13]([Cl:16])[CH:14]=2)[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:18])=[C:6]([F:17])[CH:7]=2.Br[CH2:22][C:23]#[N:24].CC(C)([O-])C.[Li+]>C1COCC1>[NH2:1][C:2]1([CH2:19][O:20][CH2:22][C:23]#[N:24])[C:15]2[C:10](=[N:11][CH:12]=[C:13]([Cl:16])[CH:14]=2)[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:18])=[C:6]([F:17])[CH:7]=2

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 67382973(5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methanol

Product 1

HCID 673831682-((5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methoxy)acetonitrileYield 43.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methanol (2.83 g, 7.87 mmol) and bromoacetonitrile (5.48 mL, 79 mmol) in 16 mL THF was heated to 40° C. and treated drop wise with lithium tert-butoxide [1N in THF (79 mL, 79 mmol)] over a time period of 4 hours. After completed addition the reaction mixture was concentrated under reduced pressure. Purification of the crude residue by column chromatography [0-40% (95:5 EtOAc/MeOH)/DCM] gave 2-((5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methoxy)acetonitrile (1.362 g, 3.42 mmol, 43.4% yield).

Workup

  1. additionaddition the reaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. customPurification of the crude residue by column chromatography [0-40% (95:5 EtOAc/MeOH)/DCM]

Sources & evidence

ORD record
ord-b95230b553ee4b0b87ab1721a5504f94
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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