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 1093850노트

반응식

HRID 1093850 반응식
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

참가 물질

9

반응물 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

생성물 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}-amide수율 70.3%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f95d5e87edf44bb5aa58caafee513f47
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

반응 노트

불러오는 중…