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

HRID 217524ノート

反応式

HRID 217524 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-28f3fe5394bb45a0ac3a4a90fd4db27f
出典データセット
uspto-grants-2012_06
特許番号
US08193365B2

反応ノート

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