Water → HCID 178502394, 화합물

HRID 1776032노트

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HRID 1776032 반응식
Br[C:2]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:5]([NH2:6])=[C:4]([F:13])[CH:3]=1.[CH3:14][O:15][C:16](=[O:49])[NH:17][C@H:18]([C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]1[NH:30][CH:31]=[C:32]([C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:35]=2)[N:33]=1)=[O:23])[CH:19]([CH3:21])[CH3:20].C1(C)C=CC=CC=1.O.C(=O)([O-])[O-].[K+].[K+]>[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>[CH3:14][O:15][C:16](=[O:49])[NH:17][C@H:18]([C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]1[NH:30][CH:31]=[C:32]([C:34]2[CH:35]=[CH:36][C:37]([C:2]3[CH:3]=[C:4]([F:13])[C:5]([NH2:6])=[CH:7][C:8]=3[C:9]([F:12])([F:11])[F:10])=[CH:38][CH:39]=2)[N:33]=1)=[O:23])[CH:19]([CH3:21])[CH3:20]

참가 물질

7

반응물 5

HCID 962WaterHCID 1140TolueneHCID 11430Potassium CarbonateHCID 70180464-Bromo-2-fluoro-5-(trifluoromethyl)anilineHCID 178502353HCID 178502353, 화합물

생성물 1

HCID 178502394HCID 178502394, 화합물수율 77.4%

시약·촉매·용매 1

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매

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온도
100 °C

실험 절차

A mixture of 4-bromo-2-fluoro-5-(trifluoromethyl)aniline (78 mg, 0.302 mmol) and [(S)-2-methyl-1-((S)-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (150 mg, 0.302 mmol) in toluene (0.6 mL, 6 mmol) and water (0.4 mL, 20 mmol) was purged with nitrogen. Potassium carbonate (208.8 g, 1.511 mmol) and tetrakis(triphenylphosphine)-palladium(0) (35 mg, 0.030 mmol) were added under an atmosphere of nitrogen. The reaction mixture was capped and heated at 100° C. overnight, cooled to RT, and partitioned between ethyl acetate (5.0 mL) and water (1.5 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated to give a yellowish oil, which was purified by silica gel chromatography (12 g silica gel, 0-100% EtOAc/hexanes). Desired fractions were combined and concentrated to give the title intermediate as a yellowish solid (128 mg, 77% yield). (m/z): [M+H]+ calcd for C27H24F4N5O3 548.22 found 548.6.

후처리

  1. customwas purged with nitrogen
  2. customThe reaction mixture was capped
  3. temperaturecooled to RT
  4. custompartitioned between ethyl acetate (5.0 mL) and water (1.5 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a yellowish oil, which
  9. customwas purified by silica gel chromatography (12 g silica gel, 0-100% EtOAc/hexanes)
  10. concentrationconcentrated

출처 및 근거

ORD 기록
ord-2861e47cb01b429aa17def51b4713823
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09260414B2

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