Dimethylformamide → 3-(4-Hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-propionamide

HRID 1178071

反応式

HRID 1178071 の反応式
CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]([NH:21][CH2:22][C:23]([OH:25])=O)=[O:20])=[CH:13][CH:12]=1.C1C=CC2N([OH:35])N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[N:49]1([C:55]([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=2[C:63]([F:66])([F:65])[F:64])=[O:56])[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1.CN([CH:70]=[O:71])C>O>[F:64][C:63]([F:66])([F:65])[C:70]([OH:71])=[O:35].[OH:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:17][CH2:18][C:19]([NH:21][CH2:22][C:23](=[O:25])[N:52]2[CH2:53][CH2:54][N:49]([C:55](=[O:56])[C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=3[C:63]([F:66])([F:64])[F:65])[CH2:50][CH2:51]2)=[O:20])=[CH:15][CH:16]=1

参加物

9

反応物 6

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 577651N-[(4-Hydroxybenzoyl)acetyl]glycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167337831-(2-Trifluoromethylbenzoyl)piperazine hydrochloride

生成物 2

HCID 6422Trifluoroacetic acid収率 0.1%HCID 595596673-(4-Hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-propionamide収率 58.25%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

DIPEA (145 mg, 0.194 mL, 1.12 mmol) was added to a stirred solution of [3-(4-hydroxy-phenyl)propionylamino]-acetic acid (50 mg, 0.22 mmol) in DMF (4 mL). HOBT (33.3 mg, 0.25 mmol) and EDCI.HCl (107 mg, 0.56 mmol) were added at room temperature. After 2 minutes piperazine-1-yl-(2-trifluoromethyl-phenyl)-methanone hydrochloride (72.6 mg, 0.25 mmol) was added. The resulting mixture was stirred at room temperature for 24 hours. 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-Eclipse-XDB-C18-9.4×250 mm, 5 μm, mobile phase: A-0.1% Trifluoroacetic acid, B-Acetonitrile, Flow: 7 ml/min) afforded 60 mg (58.25% yield) of 3-(4-Hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-propionamide as a pale white crystalline solid (60 mg). LC-MS purity: 91.16%, HPLC purity: 98.8%. 1H NMR (DMSO): δ 9.2 (s, 1H,), 8.0 (t, 1H), 7.92-7.8 (m, 2H), 7.7 (t, 1H), 7.56 (d, 1H), 7.0 (d, 2H), 6.66 (d, 2H), 4.08-3.94 (d, 2H), 3.84-3.68 (m, 2H), 3.66-3.5 (bs, 4H), 3.2-3.1 (bd, 2H), 2.7 (bs, 2H), 2.4 (t, 2H).

後処理

  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

出典と根拠

ORDレコード
ord-3ee327f6e16e49deac7e31fee8edd8e8
出典データセット
uspto-grants-2010_11
特許番号
US07842696B2

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