Sodium Carbonate → N-[6-Chloro-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-3,5-bis-trifluoromethyl-benzamide

HRID 878056노트

반응식

HRID 878056 반응식
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=2)=[C:4](I)[CH:3]=1.[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[C:30]([CH3:37])[CH:29]=1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])(O)=O.[Na+]>COCCOC.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=2)=[C:4]([C:31]2[CH:32]=[CH:33][C:28]([F:27])=[CH:29][C:30]=2[CH3:37])[CH:3]=1

참가 물질

8

반응물 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 2734665(4-Fluoro-2-methylphenyl)boronic acidHCID 86670718HCID 86670718, 화합물

생성물 1

HCID 86670717N-[6-Chloro-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-3,5-bis-trifluoromethyl-benzamide

시약·촉매·용매 2

HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of N-(6-chloro-4-iodo-pyridin-3-yl)-N-methyl-3,5-bis-trifluoromethyl-benzamide (200 mg, 393 μmol) in DME (4 mL) under argon atmosphere was added 4-fluoro-2-methylphenylboronic acid (66.6 mg, 433 μmol, CAS RN 39911-29-8) and 2M aqueous Na2CO3 solution (1 mL). The reaction mixture was stirred for 15 minutes. Pd(II)acetate (4.41 mg, 19.7 μmol) and triphenylphosphine (10.3 mg, 39.3 μmol) were added and the reaction was stirred at 90° C. for 18 hours. The reaction mixture was poured on 10% aqueous NaHCO3 solution (30 mL) and 30 mL EtOAc. The layers were separated and the aqueous layer was extracted a second time with 30 mL EtOAc. The combined organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The compound was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). Colorless solid (157 mg, 81.3%). MS (TurboSpray): m/z=491.075 [M+H]+.

후처리

  1. stirringthe reaction was stirred at 90° C. for 18 hours
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted a second time with 30 mL EtOAc
  4. washThe combined organic layers were washed with 30 mL brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe compound was purified by silica gel chromatography
  9. washeluting with a gradient of n-heptane:EtOAc (100:0 to 50:50)

출처 및 근거

ORD 기록
ord-32944ee1d4ac4324b7f1db5a195bc5ce
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987307B2

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