Pentafluoropropionic anhydride → (R)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-2,2,3,3,3-pentafluoropropanamide

HRID 1365544

반응식

HRID 1365544 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([F:27])[CH:18]=2)([NH2:16])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.FC(F)(C(F)(F)F)C([O:32][C:33](=O)[C:34]([F:40])([F:39])[C:35]([F:38])([F:37])[F:36])=O>C(Cl)Cl.N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@:8]([NH:16][C:33](=[O:32])[C:34]([F:40])([F:39])[C:35]([F:38])([F:37])[F:36])([C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:24])[F:25])[CH:20]=[C:19]([F:27])[CH:18]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1

참가 물질

5

반응물 2

HCID 67742Pentafluoropropionic anhydrideHCID 58919949(R)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine

생성물 1

HCID 58920974(R)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-2,2,3,3,3-pentafluoropropanamide수율 65.2%

시약·촉매·용매 2

HCID 1049Pyridine촉매HCID 6344Dichloromethane용매

실험 절차

To a solution of (R)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine (15 mg, 0.038 mmol), prepared by method described in Procedures 5, 6 and 7, in anhydrous DCM (0.5 mL), was added pyridine (1 drop) and 2,2,3,3,3-pentafluoropropanoic anhydride (14 mg, 0.040 mmol) at room temperature. The reaction mixture was stirred for 5 mins and the solvents removed under a stream of nitrogen. The resulting residue was diluted with MeOH (0.5 mL) and purified by preparative HPLC (YMC Sunfire 30×100 mm column, eluting with 10-90% MeOH/H2O over 10 minutes containing 0.1% TFA; 40 mL/min, monitoring at 220 nm); (R)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-2,2,3,3,3-pentafluoropropanamide (13.4 mg, 65% yield) was isolated as a colorless oil at a retention time of 12.44 min. LCMS: RT=2.12 min [M+H] 541.21 (LCMS Method 2); HPLC: RT=4.28 min, Purity 98% (HPLC Method 1) NMR: 400 MHz 1H (CDCl3) 9.60 ppm, 1 H, s; 8.36 ppm, 1 H, s; 7.75 ppm, 1H, d, J=8.0 Hz; 7.44 ppm, 1H, s; 7.34 ppm, 1H, d, J=8.0Hz; 7.30 ppm, 1H, d, J=8.0 Hz; 7.09 ppm, 4 H, m; 6.53 ppm, 2H, d, J=4.0 Hz; 3.38 ppm, 1H, d, J=12.0 Hz; 3.65 ppm, 1H, d, J=12.0 Hz.

후처리

  1. customthe solvents removed under a stream of nitrogen
  2. additionThe resulting residue was diluted with MeOH (0.5 mL)
  3. custompurified by preparative HPLC (YMC Sunfire 30×100 mm column, eluting with 10-90% MeOH/H2O over 10 minutes containing 0.1% TFA; 40 mL/min, monitoring at 220 nm)

출처 및 근거

ORD 기록
ord-d97839a4643448629613eaf5a292241d
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07888376B2

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