Hydrochloric Acid → HCID 86715519、化合物

HRID 2284605ノート

反応式

HRID 2284605 の反応式
[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

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 2723981Borane;tetrahydrofuranHCID 86715520HCID 86715520、化合物

生成物 1

HCID 86715519HCID 86715519、化合物収率 78.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-7b526cde5753408abae04809a58862b6
出典データセット
uspto-grants-2015_09
特許番号
US09145433B2

反応ノート

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