3-Aminopyridine → 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(3-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093879ノート

反応式

HRID 1093879 の反応式
CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[CH:41]=[C:40]([C:42]([NH:44][CH2:45][C:46]([OH:48])=O)=[O:43])[N:39]=[N:38]2)[CH:32]=1.NC1C=NC=CC=1.Cl.[F:57][C:58]1[CH:59]=[C:60]([CH:68]=[C:69]([C:71]([F:74])([F:73])[F:72])[CH:70]=1)[O:61][CH:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1>CN(C=O)C>[F:57][C:58]1[CH:59]=[C:60]([CH:68]=[C:69]([C:71]([F:73])([F:72])[F:74])[CH:70]=1)[O:61][CH:62]1[CH2:63][CH2:64][N:65]([C:46](=[O:48])[CH2:45][NH:44][C:42]([C:40]2[N:39]=[N:38][N:37]([C:33]3[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=3)[CH:41]=2)=[O:43])[CH2:66][CH2:67]1

参加物

8

反応物 6

HCID 100093-AminopyridineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 665915174-(3-Fluoro-5-trifluoromethyl-phenoxy)-piperidine hydrochlorideHCID 66592012[(1-pyridin-3-yl-1H-[1,2,3]triazole-4-carbonyl)-amino]-acetic acid

生成物 1

HCID 578744801-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(3-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide収率 32%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

DIPEA (97 mg, 0.75 mmol) followed by HOBt (35 mg, 0.26 mmol) and EDCI (50 mg, 0.26 mmol) were added to a stirred solution of [(1-pyridin-3-yl-1H-[1,2,3]triazole-4-carbonyl)-amino]-acetic acid (prepared by the method used for the synthesis of Intermediate 64, starting from 3-aminopyridine, and subsequently, application of Step 3 of the General Scheme) (62 mg, 0.25 mmol) in DMF (3 mL). After 2 minutes of stirring, 4-(3-fluoro-5-trifluoromethyl-phenoxy)-piperidine hydrochloride (prepared by the method used for the synthesis of Intermediate 15) (75 mg, 0.25 mmol) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was partitioned between cold water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (using silica gel 60-120 and 40% EtOAc in hexane as eluent) afforded 38.5 mg (32% Yield) of 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(3-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 493, 98%. 1H NMR (300 MHz, DMSO-d6): δ 9.43 (s, 1H), 9.2 (d, 1H), 8.75 (d, 1H), 8.5 (t, 1H), 7.7 (m, 1H), 7.26 (m, 3H), 4.85 (m, 1H), 4.3 (m, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.4 (m, 1H), 3.3 (m, 1H), 2.0 (m, 2H), 1.6 (m, 2H).

後処理

  1. customprepared by the method
  2. additionwas added
  3. stirringthe resulting mixture was stirred at room temperature overnight
  4. customThe reaction mixture was partitioned between cold water and ethyl acetate
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography (using silica gel 60-120 and 40% EtOAc in hexane as eluent)

出典と根拠

ORDレコード
ord-6ebafd640dc24ee89927b035f16e901c
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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