m-Toluidine → 1-m-tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide

HRID 1093785ノート

反応式

HRID 1093785 の反応式
CCN(C(C)C)C(C)C.[C:10]1([CH3:24])[CH:15]=[CH:14][CH:13]=[C:12]([N:16]2[CH:20]=[C:19]([C:21]([OH:23])=O)[N:18]=[N:17]2)[CH:11]=1.CC1C=C(C=CC=1)N.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:55][CH2:56][C:57]([N:59]1[CH2:64][CH2:63][CH:62]([O:65][C:66]2[CH:71]=[CH:70][CH:69]=[C:68]([C:72]([F:75])([F:74])[F:73])[CH:67]=2)[CH2:61][CH2:60]1)=[O:58]>CN(C=O)C.CO.CCCCCC.O>[O:58]=[C:57]([N:59]1[CH2:60][CH2:61][CH:62]([O:65][C:66]2[CH:71]=[CH:70][CH:69]=[C:68]([C:72]([F:75])([F:73])[F:74])[CH:67]=2)[CH2:63][CH2:64]1)[CH2:56][NH:55][C:21]([C:19]1[N:18]=[N:17][N:16]([C:12]2[CH:11]=[C:10]([CH3:24])[CH:15]=[CH:14][CH:13]=2)[CH:20]=1)=[O:23]

参加物

11

反応物 6

HCID 7934m-ToluidineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 287432311-(3-methylphenyl)-1H-1,2,3-triazole-4-carboxylic acidHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

生成物 1

HCID 578744291-m-tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide収率 70.5%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8058Hexane溶媒

実験手順

DIPEA (171 mg, 1.32 mmol) was added to a stirred solution of 1-m-Tolyl-1H-[1,2,3]triazole-4-carboxylic acid (60 mg, 0.29 mmol) (prepared by the method used for the synthesis of Intermediate 64, starting from 3-methylaniline) in DMF (5 mL) followed by HOBt (44 mg, 0.32 mmol) and EDCI (141 mg, 0.73 mmol). After 2 minutes of stirring, 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (110 mg, 0.32 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. Cold water was then added and the solid was collected to afford the crude solid. The crude solid obtained was purified by recrystallisation from a solvent system (3:7:0.2), EtOAc:hexane:MeOH to afford 100 mg (70.5% Yield) of 1-m-tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 488, 96.08%. 1H NMR (300 MHz, DMSO-d6): δ 9.3 (s, 1H), 8.5 (t, 1H), 7.84 (s, 1H), 7.8 (d, 1H), 7.56-7.44 (m, 2H), 7.38-7.24 (m, 4H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (s, 1H), 3.8 (s, 1H), 3.5 (s, 1H), 3.3 (s, 1H), 2.4 (s, 3H), 2.1 (t, 2H), 1.8 (d, 2H).

後処理

  1. customprepared by the method
  2. additionwas added
  3. stirringthe resulting mixture was stirred at ambient temperature overnight
  4. customthe solid was collected
  5. customto afford the crude solid
  6. customThe crude solid obtained
  7. customwas purified by recrystallisation from a solvent system (3:7:0.2), EtOAc

出典と根拠

ORDレコード
ord-d3013f9489194b6189303b14d644f6e6
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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