Dimethylformamide → 2-(4-hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-acetamide

HRID 1178067노트

반응식

HRID 1178067 반응식
CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([NH:20][CH2:21][C:22]([OH:24])=O)=[O:19])=[CH:13][CH:12]=1.C1C=CC2N([OH:34])N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[N:48]1([C:54]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=2[C:62]([F:65])([F:64])[F:63])=[O:55])[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1.CN([CH:69]=[O:70])C>O>[F:63][C:62]([F:65])([F:64])[C:69]([OH:70])=[O:34].[OH:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:17][C:18]([NH:20][CH2:21][C:22](=[O:24])[N:51]2[CH2:52][CH2:53][N:48]([C:54](=[O:55])[C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=3[C:62]([F:65])([F:63])[F:64])[CH2:49][CH2:50]2)=[O:19])=[CH:15][CH:16]=1

참가 물질

9

반응물 6

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 4407324-HydroxyphenylacetylglycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167337831-(2-Trifluoromethylbenzoyl)piperazine hydrochloride

생성물 2

HCID 6422Trifluoroacetic acid수율 0.1%HCID 595596192-(4-hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-acetamide수율 45%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

DIPEA (0.407 g, 0.545 mL, 3.15 mmol) was added to a stirred solution of [2-(4-Hydroxy-phenyl)-acetyl amino]-acetic acid (55 mg, 0.26 mmol) in DMF (5 mL). HOBT (39 mg, 2.8 mmol) and EDCI.HCl (110 mg, 0.57 mmol) were added at room temperature. After 2 minutes, piperazine-1-yl-(2-trifluoromethyl-phenyl)-methanone hydrochloride (85.2 mg, 0.29 mmol) was added. The resulting mixture was stirred at room temperature overnight. Water was then added, and the product was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification by preparative HPLC (Column: Zorbax-XDB-9.4×250 mm, 5 μm, mobile phase: A, 0.1% Trifluoroacetic acid, B-Acetonitrile, Flow: 7 ml/min) afforded 68 mg (45% yield) of 2-(4-hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-acetamide as a white crystalline solid. LC-MS purity: 94.32%, HPLC purity: 98.38%. 1H NMR (DMSO): δ 9.4 (s, 1H,), 8.0 (t, 1H), 7.9-7.7 (m, 2H), 7.65 (t, 1H), 7.5 (d, 1H), 7.0 (d, 2H), 6.6 (d, 2H), 4.04-3.9 (d, 2H), 3.7-3.5 (m, 4H), 3.25 (m, 4H), 3.0 (m, 2H).

후처리

  1. extractionthe product was extracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford the crude product
  6. customPurification by preparative HPLC (Column

출처 및 근거

ORD 기록
ord-3043987c371c42c88b81980ba43f28c1
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842696B2

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