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 528881Notes

Reaction equation

HRID 528881 reaction equation
[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]

Participants

7

Reactant 3

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

Product 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-carboxamideYield 24%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-2658f47fa09f450295ac00cc724aafd9
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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