Diisopropylethylamine → 2-[3,5-bis(trifluoromethyl)phenyl]-N-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}acetamide

HRID 17081

반응식

HRID 17081 반응식
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]([CH2:13][C:14](O)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:52]([C:55]1[CH:56]=[CH:57][C:58]([O:73][CH3:74])=[C:59]([C:61]2[CH:66]=[CH:65][C:64]([C:67]([F:70])([F:69])[F:68])=[CH:63][C:62]=2[CH2:71][NH2:72])[CH:60]=1)([CH3:54])[CH3:53]>C(Cl)Cl.CCOC(C)=O>[F:1][C:2]([F:17])([F:18])[C:3]1[CH:4]=[C:5]([CH2:13][C:14]([NH:72][CH2:71][C:62]2[CH:63]=[C:64]([C:67]([F:68])([F:69])[F:70])[CH:65]=[CH:66][C:61]=2[C:59]2[CH:60]=[C:55]([CH:52]([CH3:54])[CH3:53])[CH:56]=[CH:57][C:58]=2[O:73][CH3:74])=[O:15])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 1235873,5-Bis(trifluoromethyl)phenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 591351271-[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine

생성물 1

HCID 866153972-[3,5-bis(trifluoromethyl)phenyl]-N-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}acetamide

시약·촉매·용매 2

HCID 6344Dichloromethane용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

A solution of 3,5-bis(trifluoromethyl)phenylacetic acid (105.3 mg, 0.387 mmol) in CH2Cl2 (5 mL) was cooled to 0° C. N,N-diisopropylethylamine (169 μL, 0.968 mmol) was added, followed by HATU (139 mg, 0.3667 mmol). The reaction was stirred at 0° C. for 2 minutes and then a solution of 1-[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine (62.5 mg, 0.193 mmol) in CH2Cl2 (2 mL) was added. The reaction was stirred for 1 hour at 0° C. and then diluted with EtOAc (75 mL). The organics were washed with saturated NaHCO3 and brine (25 mL each), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 100% CH2Cl2 gave 2-[3,5-bis(trifluoromethyl)phenyl]-N-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}acetamide. Rf=0.26 (25% EtOAc/hexanes). LCMS=578.2 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.79 (s, 1H), 7.70 (s, 2H), 7.59 (m, 2H), 7.33 (d, J=8.5 Hz, 1H), 7.25 (m, 1H), 6.97 (d, J=2.0 Hz, 1H), 6.91 (d, J=8.5 Hz, 1H), 5.84 (bs, 1H), 4.48 (dd, J=15.1, 6.6 Hz, 1H), 4.20 (dd, J=14.9, 4.3 Hz, 1H), 3.69 (s, 3H), 3.55 (s, 2H), 2.88 (m, 1H), 1.24 (d, J=6.8 Hz, 6H).

후처리

  1. stirringThe reaction was stirred for 1 hour at 0° C.
  2. washThe organics were washed with saturated NaHCO3 and brine (25 mL each)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography with 100% CH2Cl2

출처 및 근거

ORD 기록
ord-2b7cfc63e7c24aaeb5f2a42ef60cdef5
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737295B2

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