Sodium Carbonate → Methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate

HRID 2410756노트

반응식

HRID 2410756 반응식
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:18][C:19]1[C:28](Br)=[N:27][C:26]([Br:30])=[CH:25][C:20]=1[C:21]([O:23][CH3:24])=[O:22].C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:18][C:19]1[C:28]([C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:10][CH:11]=2)=[N:27][C:26]([Br:30])=[CH:25][C:20]=1[C:21]([O:23][CH3:24])=[O:22]

참가 물질

5

반응물 3

HCID 10340Sodium CarbonateHCID 27343144-Benzyloxy-phenylboronic acidHCID 53419616Methyl 3-amino-2,6-dibromoisonicotinate

생성물 1

HCID 86663009Methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate수율 62%

시약·촉매·용매 1

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매

실험 절차

A mixture of 4-(benzyloxy)phenylboronic acid (3.53 g, 15.5 mmol), methyl 3-amino-2,6-dibromoisonicotinate (4.0 g, 12.9 mmol), tetrakis(triphenylphosphine)-palladium(0) (0.90 g, 0.77 mmol), sodium carbonate (3.28 g, 31.0 mmol) was flushed with nitrogen and toluene (32 mL), and MeOH (11 mL) were added. The reaction was heated at reflux under nitrogen for 24 hr. It was partitioned between EtOAc and water. The organic phase was washed with brine, dried with sodium sulfate and the solvent removed. Radial chromatography (step gradient elution with hexane containing 20 to 80% DCM) afforded methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate (3.28 g, 7.94 mmol, 62% yield) as a yellow solid. MS (ESI) m/z 415.0 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 7.77 (1H, s), 7.52-7.58 (2H, m), 7.41-7.46 (2H, m), 7.36-7.41 (2H, m), 7.30-7.36 (1H, m), 7.04-7.09 (2H, m), 5.95 (2H, br. s.), 3.92 (3H, s).

후처리

  1. customwas flushed with nitrogen and toluene (32 mL), and MeOH (11 mL)
  2. additionwere added
  3. temperatureThe reaction was heated
  4. temperatureat reflux under nitrogen for 24 hr
  5. customIt was partitioned between EtOAc and water
  6. washThe organic phase was washed with brine
  7. dry with materialdried with sodium sulfate
  8. customthe solvent removed
  9. washRadial chromatography (step gradient elution with hexane containing 20 to 80% DCM)

출처 및 근거

ORD 기록
ord-a80e3ffe1dac4e5abf426dbd9614ee54
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815840B2

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