Trimethylaluminum → 7-Bromo-3-chloro-8-fluoro-2',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,3'-[1,4]oxazin]-5'-amine

HRID 455570Notes

Reaction equation

HRID 455570 reaction equation
[NH2:1][C:2]1([CH2:19][O:20][CH2:21][C:22]#[N:23])[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.C[Al](C)C>CC1OCCC1>[Br:18][C:5]1[CH:4]=[C:3]2[C:2]3([N:1]=[C:22]([NH2:23])[CH2:21][O:20][CH2:19]3)[C:15]3[C:10](=[N:11][CH:12]=[C:13]([Cl:16])[CH:14]=3)[O:9][C:8]2=[CH:7][C:6]=1[F:17]

Participants

4

Reactant 2

HCID 16682925TrimethylaluminumHCID 673831682-((5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methoxy)acetonitrile

Product 1

HCID 584660027-Bromo-3-chloro-8-fluoro-2',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,3'-[1,4]oxazin]-5'-amineYield 31%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-((5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methoxy)acetonitrile (1.363 g, 3.42 mmol) in 10 mL 2-MeTHF under nitrogen atmosphere was added trimethylaluminum [2N in heptane (3.42 mL, 6.84 mmol)]. After stirring for 10 minutes, the reaction mixture was heated to 80° C. overnight. The reaction mixture was then allowed to cool to RT, and quenched with MeOH. Saturated Rochelle's salt solution was added, and the reaction mixture was vigorously stirred for an additional hour. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated under reduced pressure. Purification of the crude residue by column chromatography [0-80% (90:10:1 DCM/MeOH/NH4OH)/DCM] gave 7-bromo-3-chloro-8-fluoro-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.422 g, 1.059 mmol, 31.0% yield).

Workup

  1. temperatureto cool to RT
  2. customquenched with MeOH
  3. additionSaturated Rochelle's salt solution was added
  4. stirringthe reaction mixture was vigorously stirred for an additional hour
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customPurification of the crude residue by column chromatography [0-80% (90:10:1 DCM/MeOH/NH4OH)/DCM]

Sources & evidence

ORD record
ord-3b0b67da85524b8dbd47dcedc7aecc3d
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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