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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
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HRID 528881 반응식
[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]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 3

HCID 81531DiisopropylethylamineHCID 710621452-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid2회HCID 86718905N,N-dimethyl-2,5-dihydro-1H-benzo[e][1,3]diazepin-3-amine

생성물 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
수율 24%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 111,2-Dichloroethane용매HCID 8028Tetrahydrofuran용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-2658f47fa09f450295ac00cc724aafd9
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09346795B2

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