Hydrochloric Acid → HCID 86715519, 화합물

HRID 2284605노트

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HRID 2284605 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

HCID 86715519HCID 86715519, 화합물수율 78.8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
80 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-7b526cde5753408abae04809a58862b6
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09145433B2

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