1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093850ノート

反応式

HRID 1093850 の反応式
CCN(C(C)C)C(C)C.[N:10]1([N:16]2[CH:20]=[C:19]([C:21]([OH:23])=O)[N:18]=[N:17]2)[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.NN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:53][CH2:54][C:55]([N:57]1[CH2:62][CH2:61][CH:60]([O:63][C:64]2[CH:69]=[C:68]([F:70])[CH:67]=[CH:66][C:65]=2[Cl:71])[CH2:59][CH2:58]1)=[O:56]>CN(C=O)C.O>[Cl:71][C:65]1[CH:66]=[CH:67][C:68]([F:70])=[CH:69][C:64]=1[O:63][CH:60]1[CH2:61][CH2:62][N:57]([C:55](=[O:56])[CH2:54][NH:53][C:21]([C:19]2[N:18]=[N:17][N:16]([N:10]3[CH2:11][CH2:12][O:13][CH2:14][CH2:15]3)[CH:20]=2)=[O:23])[CH2:58][CH2:59]1

参加物

9

反応物 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 20315N-AminomorpholineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 665915752-Amino-1-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 665919181-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid

生成物 1

HCID 442350251-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide収率 70.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

DIPEA (200 mg, 1.54 mmol) was added to a stirred solution of 1-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid (prepared by the method used for the synthesis of Intermediate 64, starting from 4-aminomorpholine) (70 mg, 0.35 mmol) in DMF (5 mL) followed by HOBt (52 mg, 0.38 mmol) and EDCI (170 mg, 0.88 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (125 mg, 0.38 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the precipitate was collected. The solid was purified by recrystallizing from a mixture of 20% ethyl acetate in hexane and MeOH to afford 116 mg (70.3% Yield) of 1-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 467.15, 96.7%. 1H NMR (300 MHz, DMSO-d6): δ 8.8 (s, 1H), 8.4 (t, 1H), 7.5 (t, 1H), 7.3 (d, 1H), 6.8 (t, 1H), 4.9 (m, 1H), 4.2 (d, 2H), 3.85 (t, 4H), 3.7 (d, 2H), 3.5 (b, 2H), 3.3 (bs, 4H), 2.0 (d, 2H), 1.8 (d, 2H).

後処理

  1. customprepared by the method
  2. additionwas added
  3. stirringthe resulting mixture was stirred at room temperature overnight
  4. customthe precipitate was collected
  5. customThe solid was purified
  6. customby recrystallizing from a mixture of 20% ethyl acetate in hexane and MeOH

出典と根拠

ORDレコード
ord-f95d5e87edf44bb5aa58caafee513f47
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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