Potassium Carbonate → 1-[5-(3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-pyridin-2-yl]-piperazine

HRID 1632112노트

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HRID 1632112 반응식
COC(=O)O[CH2:5][C:6]1[C:7]([F:21])=[C:8]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1.CC1(C)C(C)(C)OB([C:31]2[CH:32]=[CH:33][C:34]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[N:35][CH:36]=2)O1.C1(P(C(P(C2C=CC=CC=2)C2C=CC=CC=2)(CC)CC)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>[CH2-]C=C.[CH2-]C=C.Cl[Pd+].Cl[Pd+].CN(C)C=O>[Cl:20][C:16]1[CH:15]=[C:14]([C:8]2[C:9]([O:12][CH3:13])=[CH:10][CH:11]=[C:6]([CH2:5][C:31]3[CH:32]=[CH:33][C:34]([N:37]4[CH2:38][CH2:39][NH:40][CH2:41][CH2:42]4)=[N:35][CH:36]=3)[C:7]=2[F:21])[CH:19]=[CH:18][CH:17]=1

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 162179462-(Piperazin-1-yl)pyridine-5-boronic acid, pinacol esterHCID 57703696Carbonic acid 3'-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl ester methyl esterHCID 87189959Bis-diphenylphosphinopentane

생성물 1

HCID 580200671-[5-(3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-pyridin-2-yl]-piperazine수율 18%

시약·촉매·용매 2

HCID 61538Palladium, di-mu-chlorobis(eta3-2-propenyl)di-촉매HCID 6228Dimethylformamide용매

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온도
85 °C

실험 절차

To carbonic acid 3′-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl ester methyl ester (0.2 g, 0.62 mmol), 1-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-yl]-piperazine (0.2 g, 0.68 mmol), bis-diphenylphosphinopentane (0.08 g, 0.18 mmol), potassium carbonate (0.26 g, 1.85 mmol) and allyl palladium (II) chloride dimer (0.034 g, 0.09 mmol) was added dimethyl formamide (6 mL). The reaction was degassed with an argon stream for 10 min. The reaction was stirred at 85° C. for 18 h. The reaction was cooled to room temperature, poured onto crushed ice-water (150 mL), filtered, washed with water, dried over sodium sulfate, filtered, and the solvent removed under vacuum. The residue was purified by silica gel column chromatography using 10% methanol in dichloromethane to afford P-423 (0.05 g, 18% yield) as light brown gummy solid. 1H NMR (400 MHz, DMSO-d6): 3.20 (br s, 3H) 3.55-3.99 (m, 10H), 6.95 (d, J=8.59 Hz, 1H), 7.11 (br s, 1H), 7.23-7.39 (m, 3H), 7.39-7.55 (m, 2H), 7.69 (br s, 1H), 8.02 (s, 1H), 9.33 (br s, 2H) ppm. Calc. 411.9; APCI+ (M+1): 412.1, 97%.

후처리

  1. customThe reaction was degassed with an argon stream for 10 min
  2. temperatureThe reaction was cooled to room temperature
  3. additionpoured
  4. customonto crushed ice-water (150 mL)
  5. filtrationfiltered
  6. washwashed with water
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customthe solvent removed under vacuum
  10. customThe residue was purified by silica gel column chromatography
  11. customto afford P-423 (0.05 g, 18% yield) as light brown gummy solid

출처 및 근거

ORD 기록
ord-deae22c6d6ef4afaaa28440fa4d10602
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791267B2

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