Ethylenediamine → 1-[4-(2,4-bis-trifluoromethyl-benzoylamino)-2-trifluoromethyl-phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide

HRID 912592

反応式

HRID 912592 の反応式
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[CH:18]=[C:17]([CH3:19])[N:16]([C:20]3[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][C:21]=3[C:27]([F:30])([F:29])[F:28])[C:15]=2[CH3:31])=[O:13])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[F:32][C:33]([F:48])([F:47])[C:34]1[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:40]=[CH:39][C:35]=1[C:36]([NH2:38])=[O:37].C([O-])([O-])=O.[K+].[K+].NCCN.[OH-].[Na+].C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O>[Cu]I.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[CH:18]=[C:17]([CH3:19])[N:16]([C:20]3[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][C:21]=3[C:27]([F:29])([F:30])[F:28])[C:15]=2[CH3:31])=[O:13])=[CH:7][CH:6]=1)(=[O:3])=[O:4].[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[CH:18]=[C:17]([CH3:19])[N:16]([C:20]3[CH:25]=[CH:24][C:23]([NH:38][C:36](=[O:37])[C:35]4[CH:39]=[CH:40][C:41]([C:43]([F:45])([F:46])[F:44])=[CH:42][C:34]=4[C:33]([F:32])([F:47])[F:48])=[CH:22][C:21]=3[C:27]([F:30])([F:29])[F:28])[C:15]=2[CH3:31])=[O:13])=[CH:7][CH:6]=1)(=[O:4])=[O:3]

参加物

11

反応物 6

HCID 3301EthylenediamineHCID 6049Ethylenediaminetetraacetic AcidHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 27360992,4-Bis(trifluoromethyl)benzamideHCID 598076331-[4-Bromo-2-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxylic acid [4-(methanesulfonyl)phenyl]-amide

生成物 2

HCID 598076331-[4-Bromo-2-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxylic acid [4-(methanesulfonyl)phenyl]-amideHCID 598077141-[4-(2,4-bis-trifluoromethyl-benzoylamino)-2-trifluoromethyl-phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide収率 39.9%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
110 °C

実験手順

1-[4-Bromo-2-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxylic acid [4-(methanesulfonyl)phenyl]-amide was prepared as described in Example 1G. Into an oven-dried 1 dram vial was added 1-[4-Bromo-2-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxylic acid [4-(methanesulfonyl)phenyl]-amide (26 mg, 50 μmol), 2,4-Bis(Trifluoromethyl)benzamide (13 mg, μmol) Copper (1) Iodide (50 mg, 260 μmol), K2CO3 (50 mg, 360 μmol), N,N′-Dimethylenediamine (9 mg, 100 μmol), and 0.4 mL of Toluene. The vial was sealed and stirred for 18 h at 110° C. The reaction was worked up by addition of a 1:1 solution of 2.0 M NaOH: 0.5M EDTA (1 ml) and Ethyl Acetate (1 ml). The vial was vortexed and the Ethyl Acetate was removed and dried in Vacuo. The crude material was purified by reverse-phase chromatography (C18 column), eluting with 0.05% TFA in MeCN/H2O (30:70 to 90:10) to yield the title compound (6.9 mg, 10%) as a white solid. 1H-NMR (DMSO-d6): δ11.24 (1H, s), 9.78 (1H, s), 8.28 (1H, d, J=2 Hz), 8.22 (1H, d, J=8 Hz), 8.19 (1H, s), 8.02 (4H, m), 7.76 (2H, d, J=9 Hz), 7.44 (2H, d, J=9 Hz), 6.59 (1H, s), 3.09 (3H, s), 2.10 (3H, s), 1.84 (3H, s); MS (ESI): 692 (MH+).

後処理

  1. customThe vial was sealed
  2. customthe Ethyl Acetate was removed
  3. customdried in Vacuo
  4. customThe crude material was purified by reverse-phase chromatography (C18 column)
  5. washeluting with 0.05% TFA in MeCN/H2O (30:70 to 90:10)

出典と根拠

ORDレコード
ord-69045874ed8f4e539e04bef84fc24ff3
出典データセット
uspto-grants-2011_09
特許番号
US08026237B2

関連ノート

読み込み中…