Hydrochloric Acid → HCID 86715519, compound

HRID 2284605Notes

Reaction equation

HRID 2284605 reaction equation
[Br:1][C:2]1[C:13]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([CH3:21])[CH:15]=2)=[N:12][C:5]2[O:6][CH2:7][C:8](=O)[N:9]([CH3:10])[C:4]=2[CH:3]=1.B.C1COCC1.Cl>C1COCC1>[Br:1][C:2]1[C:13]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([CH3:21])[CH:15]=2)=[N:12][C:5]2[O:6][CH2:7][CH2:8][N:9]([CH3:10])[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723981Borane;tetrahydrofuranHCID 86715520HCID 86715520, compound

Product 1

HCID 86715519HCID 86715519, compoundYield 78.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To the stirring solution of 7-bromo-6-(4-fluoro-3-methylphenyl)-1-methyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (595 mg) and THF (15 mL) under argon was added BH3.THF (5.1 mL, 1N solution in THF) dropwise for 20 min. After 12 h, the reaction mixture was cooled in ice-bath and transferred 1N aq. HCl (16 mL). Subsequently, cooling bath was removed and heated at 80° C. for 1 h. The reaction mixture was concentrated, basified with aq. NaHCO3 solution and extracted with EtOAc (2×125 mL). Workup of the combined organic layers followed by flash column chromatographic purification (Combiflash® companion System® with RediSep® silica gel column 24 g and 30-50% EtOAc/hexanes eluting solvent) provided 450 mg of 7-bromo-6-(4-fluoro-3-methylphenyl)-1-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine as an off-white solid. 1H NMR (300 MHz, DMSO-d6): δ 7.45-7.32 (m, 2H), 7.21 (s, 1H), 7.13 (dd, J=9.8, 8.5 Hz, 1H), 4.59-4.21 (m, 2H), 3.47-3.25 (m, 2H), 2.88 (s, 3H), 2.25 (d, J=1.9 Hz, 3H). 19F NMR (282 MHz, DMSO-d6) δ −118.92 (m).

Workup

  1. temperaturethe reaction mixture was cooled in ice-bath
  2. temperatureSubsequently, cooling bath
  3. customwas removed
  4. concentrationThe reaction mixture was concentrated
  5. extractionextracted with EtOAc (2×125 mL)
  6. customWorkup of the combined organic layers followed by flash column chromatographic purification (Combiflash® companion System® with RediSep® silica gel column 24 g and 30-50% EtOAc/hexanes eluting solvent)

Sources & evidence

ORD record
ord-7b526cde5753408abae04809a58862b6
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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