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

HRID 1093878ノート

反応式

HRID 1093878 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:66]=[C:67]([C:69]([F:72])([F:71])[F:70])[CH:68]=1)[O:61][CH:62]1[CH2:65][NH:64][CH2:63]1>CN(C=O)C>[F:57][C:58]1[CH:59]=[C:60]([CH:66]=[C:67]([C:69]([F:71])([F:70])[F:72])[CH:68]=1)[O:61][CH:62]1[CH2:65][N:64]([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])[CH2:63]1

参加物

8

反応物 6

HCID 100093-AminopyridineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66592012[(1-pyridin-3-yl-1H-[1,2,3]triazole-4-carbonyl)-amino]-acetic acidHCID 665922143-(3-Fluoro-5-trifluoromethyl-phenoxy)-azetidine hydrochloride

生成物 1

HCID 578744501-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide収率 16.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

DIPEA (143 mg, 1.1 mmol) followed by HOBt (39 mg, 0.29 mmol) and EDCI (56 mg, 0.29 mmol) was 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) (68.3 mg, 0.27 mmol) in DMF (2 mL). After 2 minutes of stirring, 3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidine hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (75 mg, 0.27 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 preparative HPLC afforded 21 mg (16.4% Yield) of 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 465, 93.03%. 1H NMR (300 MHz, DMSO-d6): δ 9.5 (s, 1H), 9.2 (d, 1H), 8.7 (m, 2H), 8.4 (m, 1H), 8.3 (s, 1H), 7.65 (m, 1H), 7.3 (d, 1H), 7.1 (m, 2H), 5.2 (m, 1H), 4.7 (m, 1H), 4.4 (m, 1H), 4.2 (m, 1H), 3.8 (m, 3H).

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 materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by preparative HPLC

出典と根拠

ORDレコード
ord-84a2c17416874d5e83cf0d54fdda988e
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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