Hydrochloric Acid → N-{4-[2-(2-Hydroxy-ethyl)-phenyl]-pyridin-3-yl}-N-methyl-3,5-bis-trifluoromethyl-benzamide

HRID 878086노트

반응식

HRID 878086 반응식
I[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N:8]([CH3:25])[C:9](=[O:24])[C:10]1[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]=1.[Si]([O:33][CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1B(O)O)(C(C)(C)C)(C)C.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>COCCOC.CCOC(C)=O>[OH:33][CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N:8]([CH3:25])[C:9](=[O:24])[C:10]1[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]=1

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 441193492-(2-(tert-Butyldimethylsilyloxy)ethyl)phenylboronic acidHCID 86670697N-(4-iodopyridin-3-yl)-N-methyl-3,5-bis(trifluoromethyl)benzamide

생성물 1

HCID 86670723N-{4-[2-(2-Hydroxy-ethyl)-phenyl]-pyridin-3-yl}-N-methyl-3,5-bis-trifluoromethyl-benzamide

시약·촉매·용매 2

HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

실험 절차

To the solution of N-(4-iodo-pyridin-3-yl)-N-methyl-3,5-bis-trifluoromethyl-benzamide (150 mg, 316 μmol, example 36, intermediate a) in DME (3 mL) was added 2-(2-(tert-butyldimethylsilyloxy)ethyl)phenylboronic acid (88.7 mg, 316 μmol, CAS RN 913835-62-8) and 2M aqueous Na2CO3 solution (1 mL). The reaction mixture was stirred under argon atmosphere for 15 minutes. Pd(II)acetate (3.55 mg, 15.8 μmol) and triphenylphosphine (8.3 mg, 31.6 μmol) were added. The reaction mixture stirred at 90° C. for 18 hours and then poured on 30 mL 1M aqueous HCl and 30 mL EtOAc. The layers were separated and the aqueous layer was extracted a second time with 30 mL EtOAc. The 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 60:40). Colorless solid (95 mg, 52%). MS (ESI): m/z=469.134 [M+H]+.

후처리

  1. stirringThe reaction mixture 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 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 60:40)

출처 및 근거

ORD 기록
ord-f908bb983780419098898be772f342a8
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987307B2

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