Sodium Carbonate → 6-Chloro-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 629095노트

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HRID 629095 반응식
[Cl:1][C:2]1[C:21](I)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.[N:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[Cl:1][C:2]1[C:21]([C:27]2[CH:28]=[N:23][CH:24]=[N:25][CH:26]=2)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1

참가 물질

5

반응물 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 867025996-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

생성물 1

HCID 722034246-Chloro-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

A mixture of 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 56.1, 5.7 g, 12.75 mmol), pyrimidine-5-boronic acid (2.5 g, 19.77 mmol), PdCl2(dppf)-(CH2Cl2) (0.625 g, 0.765 mmol), Na2CO3 (19.13 mL, 38.3 mmol) and DME (100 mL) was stirred at 80° C. for 2.5 h under argon atmosphere. The RM was filtered through Hyflo®, diluted with EtOAc (100 mL), washed with a sat. aq. solution of NaHCO3 and with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Biotage Silica gel column, 120 g, Eluent: n-hexane/EtOAc from 20% to 60% EtOAc) to give the title compound product as a pink crystalline solid. UPLC-MS (Condition 2) tR=1.01 min, 393.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.42 (d, J=8.99 Hz, 2H) 7.88 (d, J=9.38 Hz, 2H) 8.56 (d, J=2.35 Hz, 1H) 9.03 (d, J=2.35 Hz, 1H) 9.10 (s, 2H) 9.32 (s, 1H) 10.69 (s, 1H).

후처리

  1. filtrationThe RM was filtered through Hyflo®
  2. additiondiluted with EtOAc (100 mL)
  3. washwashed with a sat. aq. solution of NaHCO3 and with brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give the crude product which
  7. customwas purified by flash chromatography (Biotage Silica gel column, 120 g, Eluent: n-hexane/EtOAc from 20% to 60% EtOAc)

출처 및 근거

ORD 기록
ord-f8da881e6ade485193787a0cb89cd8f3
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315489B2

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