Boron tribromide → 6-[({1-[2-(6-Hydroxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidin-4-yl)amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 1644343Notes

Reaction equation

HRID 1644343 reaction equation
C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][C:9](=[O:12])[N:8]([CH2:13][CH2:14][N:15]3[CH2:20][CH2:19][CH:18]([NH:21][CH2:22][C:23]4[CH:24]=[CH:25][C:26]5[O:27][CH2:28][C:29](=[O:33])[NH:30][C:31]=5[N:32]=4)[CH2:17][CH2:16]3)[C:7]=2[CH:34]=1.B(Br)(Br)Br>ClCCl>[OH:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][C:9](=[O:12])[N:8]([CH2:13][CH2:14][N:15]3[CH2:20][CH2:19][CH:18]([NH:21][CH2:22][C:23]4[CH:24]=[CH:25][C:26]5[O:27][CH2:28][C:29](=[O:33])[NH:30][C:31]=5[N:32]=4)[CH2:17][CH2:16]3)[C:7]=2[CH:34]=1

Participants

4

Reactant 2

HCID 25134Boron tribromide2×HCID 15983550HCID 15983550, compound

Product 1

HCID 159838106-[({1-[2-(6-Hydroxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidin-4-yl)amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 6-[({1-[2-(6-methoxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidin-4-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 22) (100 mg, 0.21 mmol) in dichloromethane was cooled to −78° C. and treated with 1M boron tribromide (0.63 mL, 0.63 mmol) dropwise. The reaction mixture was stirred at room temperature overnight. The reaction mixture was cooled to −78° C. and an additional 1 equivalent of 1M boron tribromide was added. The reaction was stirred for 4 hours at room temperature, and then quenched with saturated sodium bicarbonate. The organic layer was separated and the aqueous phase was extracted three times with dichloromethane. The combined organic extracts were dried over magnesium sulfate and concentrated to dryness under reduced pressure to afford crude product, 11 mg (11%), as a solid.

Workup

  1. temperatureThe reaction mixture was cooled to −78° C.
  2. stirringThe reaction was stirred for 4 hours at room temperature
  3. customquenched with saturated sodium bicarbonate
  4. customThe organic layer was separated
  5. extractionthe aqueous phase was extracted three times with dichloromethane
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. concentrationconcentrated to dryness under reduced pressure
  8. customto afford crude product, 11 mg (11%)

Sources & evidence

ORD record
ord-7020cf138ca04de59a9a4d3913ffb159
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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