1-Hydroxybenzotriazole → HCID 57874482、化合物

HRID 1093756ノート

反応式

HRID 1093756 の反応式
CCN(C(C)C)C(C)C.[C:10]1([C:16]2[O:20][N:19]=[C:18]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[CH:17]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[F:51][C:52]([F:67])([F:66])[C:53]1[CH:54]=[C:55]([CH:63]=[CH:64][CH:65]=1)[O:56][CH:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1>CN(C=O)C.O>[O:27]=[C:25]([N:60]1[CH2:59][CH2:58][CH:57]([O:56][C:55]2[CH:63]=[CH:64][CH:65]=[C:53]([C:52]([F:51])([F:66])[F:67])[CH:54]=2)[CH2:62][CH2:61]1)[CH2:24][NH:23][C:21]([C:18]1[CH:17]=[C:16]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[O:20][N:19]=1)=[O:22]

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 433543392-[(5-Phenyl-1,2-oxazol-3-yl)formamido]acetic acidHCID 467356844-[3-(Trifluoromethyl)phenoxy]piperidine hydrochloride

生成物 1

HCID 57874482HCID 57874482、化合物収率 51.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

DIPEA (96 mg, 0.745 mmol) was added to a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (67 mg, 0.27 mmol) in DMF (3 mL) followed by HOBt (36 mg, 0.273 mmol) and EDCI.HCl (62 mg, 0.32 mmol). After 2 minutes 4-(3-trifluoromethyl-phenoxy)-piperidine hydrochloride (70 mg, 0.248 mmol) (prepared by method used for the synthesis of Intermediate 15) was added to the reaction mixture and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure The residue was purified by column chromatography (using 60-120 silica gel and 50% EtOAc in hexane as eluent) to afford 60 mg (34% Yield) of 5-phenyl-isoxazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 474, 70.17%. 1H NMR (300 MHz, DMSO-d6): δ8.7-8.6 (t, 1H), 8.0-7.9 (m, 2H), 7.6-7.5 (m, 4H), 7.4 (s, 1H), 7.3-7.26 (t, 3H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.5 (m, 1H), 3.3 (m, 1H), 2.0 (m, 2H), 1.8-1.4 (m, 2H).

後処理

  1. additionwas added to the reaction mixture
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure The residue
  5. customwas purified by column chromatography (using 60-120 silica gel and 50% EtOAc in hexane as eluent)

出典と根拠

ORDレコード
ord-2873809a451549d597bcf8808026e09e
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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