1-Hydroxybenzotriazole → N-(2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-4-phenylamino-benzamide

HRID 1093595ノート

反応式

HRID 1093595 の反応式
[C:1]1([NH:7][C:8]2[CH:20]=[CH:19][C:11]([C:12]([NH:14][CH2:15][C:16]([OH:18])=O)=[O:13])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH3:53][N:54]([CH:65]1[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=1[C:61]([F:64])([F:63])[F:62]>CN(C=O)C.O>[CH3:53][N:54]([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=1[C:61]([F:64])([F:62])[F:63])[CH:65]1[CH2:70][CH2:69][N:68]([C:16](=[O:18])[CH2:15][NH:14][C:12](=[O:13])[C:11]2[CH:10]=[CH:9][C:8]([NH:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:20][CH:19]=2)[CH2:67][CH2:66]1

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57874498(4-Phenylamino-benzoylamino)-acetic acidHCID 66591695N-Methyl-N-(2-(trifluoromethyl)phenyl)piperidin-4-amine hydrochloride

生成物 1

HCID 44235734N-(2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-4-phenylamino-benzamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a stirred solution of (4-phenylamino-benzoylamino)-acetic acid (0.051 g, 0.00019 mol) in DMF (5 mL) was added DIPEA (0.061 g, 0.00048 mol), HOBt (0.025 g, 0.00019 mol) and EDCI.HCl (0.076 g, 0.00040 mol) at ambient temperature. After 2 minutes methyl-piperidin-4-yl-(2-trifluoromethyl-phenyl)-amine hydrochloride (0.047 g, 0.00016 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative HPLC [(column-Zorbax SB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/Acetonitrile (B), gradient: (Time): (% B)-0:30; 2:50; 8:80)]) to afford 0.031 (38%) of N-(2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-4-phenylamino-benzamide. LCMS: 511.22 (M+1)+, 99.08%, 1H NMR (DMSO-d6): δ 8.6 (s, 1H), 8.2 (t, 1H), 7.8 (d, 2H), 7.7 (m, 3H), 7.4 (m, 3H), 7.2 (d, 2H), 7.1 (d, 2H), 6.9 (t, 1H), 4.4 (d, 1H), 4.1 (d, 2H), 3.9 (d, 1H), 3.1 (m, 3H), 2.6 (s, 4H), 1.8 (d, 2H), 1.4 (m, 1H).

後処理

  1. extractionthe product was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with brine solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC [(column-Zorbax SB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/Acetonitrile (B)

出典と根拠

ORDレコード
ord-f91220b5bc18411c9cd3c01a11fa1e8e
出典データセット
uspto-grants-2012_03
特許番号
US08129376B2

反応ノート

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