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Diisopropylethylamine → N,N-Dibutyl-4-chloro-1-(2-(3-(dimethylamino)-2,5-dihydro-1H-benzo[e][1,3]diazepine-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide

HRID 528881
ノート
印刷プレビュー

反応式

HRID 528881 の反応式
[Cl:1][C:2]1[C:3]([C:33](=[O:43])[N:34]([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH2:37][CH3:38])=[N:4][N:5]([C:8]2[CH:16]=[CH:15][C:14]([C:17](=[O:32])[NH:18][S:19]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)(=[O:21])=[O:20])=[CH:13][C:9]=2[C:10]([OH:12])=O)[C:6]=1[CH3:7].[CH3:44][N:45]([CH3:57])[C:46]1[NH:52][CH2:51][C:50]2[CH:53]=[CH:54][CH:55]=[CH:56][C:49]=2[CH2:48][N:47]=1.C(N(C(C)C)C(C)C)C>ClCCCl.C1COCC1.CN(C1C=CN=CC=1)C>[CH2:35]([N:34]([CH2:39][CH2:40][CH2:41][CH3:42])[C:33]([C:3]1[C:2]([Cl:1])=[C:6]([CH3:7])[N:5]([C:8]2[CH:16]=[CH:15][C:14]([C:17](=[O:32])[NH:18][S:19]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)(=[O:20])=[O:21])=[CH:13][C:9]=2[C:10]([N:52]2[CH2:51][C:50]3[CH:53]=[CH:54][CH:55]=[CH:56][C:49]=3[CH2:48][N:47]=[C:46]2[N:45]([CH3:57])[CH3:44])=[O:12])[N:4]=1)=[O:43])[CH2:36][CH2:37][CH3:38]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 81531DiisopropylethylamineHCID 710621452-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid2 回HCID 86718905N,N-dimethyl-2,5-dihydro-1H-benzo[e][1,3]diazepin-3-amine

生成物 1

HCID 71062236N,N-Dibutyl-4-chloro-1-(2-(3-(dimethylamino)-2,5-dihydro-1H-benzo[e][1,3]diazepine-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide
収率 24%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 111,2-Dichloroethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 2-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid (Intermediate 91F, 36 mg, 0.058 mmol) in DCE (1.0 mL) was added 1-chloro-N,N-2-trimethylprop-1-en-1-amine (15 μL, 0.12 mmol). The resulting reaction mixture was stirred at room temperature for 1.5 h. A solution of N,N-dimethyl-2,5-dihydro-1H-benzo[e][1,3]diazepin-3-amine (Rodriguez, H. R. et al., J. Org. Chem., 33:670-676 (1968)) (11 mg, 0.058 mmol) in THF (1.0 mL) was then added, followed by DMAP (7 mg, 0.058 mmol) and i-Pr2EtN (50 μL, 0.29 mmol). The resulting reaction mixture was stirred at room temperature for 12 h, then concentrated in vacuo and purified by preparative HPLC to give the title compound (11 mg, 24%). 1H NMR (DMSO-d6, mixture of amide rotamers) δ 10.31 (br s, 1H), 8.56 (br s, 1H), 8.32-7.87 (m, 7H), 7.77-7.57 (m, 2.5H), 7.33-7.05 (m, 3H), 6.98 (br s, 0.5H), 5.09-4.53 (m, 3H), 4.08 (br s, 2H), 3.86-2.85 (m, 9H), 2.14 (s, 3H), 1.71-1.41 (m, 3H), 1.36-1.07 (m, 3H), 0.99-0.80 (m, 4.5H), 0.54 (br s, 3.5H); MS(ESI+) m/z 796.8 (M+H)+.

後処理

  1. customThe resulting reaction mixture
  2. customThe resulting reaction mixture
  3. stirringwas stirred at room temperature for 12 h
  4. concentrationconcentrated in vacuo
  5. custompurified by preparative HPLC

出典と根拠

ORDレコード
ord-2658f47fa09f450295ac00cc724aafd9
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09346795B2

反応ノート

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