1,2-Dichloroethane → N3-(2-Aminobenzyl)-4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-N1-(naphthalen-2-ylsulfonyl)isophthalamide

HRID 528865Notes

Reaction equation

HRID 528865 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](O)=[O:11])[C:6]=1[CH3:7].[NH2:44][CH2:45][C:46]1[CH:52]=[CH:51][CH:50]=[CH:49][C:47]=1[NH2:48].C(Cl)CCl.ON1C2N=CC=CC=2N=N1>C(Cl)Cl.CN(C=O)C>[NH2:48][C:47]1[CH:49]=[CH:50][CH:51]=[CH:52][C:46]=1[CH2:45][NH:44][C:10](=[O:11])[C:9]1[CH:13]=[C:14]([CH:15]=[CH:16][C:8]=1[N:5]1[C:6]([CH3:7])=[C:2]([Cl: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]1)[C:17]([NH:18][S:19]([C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=1)(=[O:21])=[O:20])=[O:32]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 1780962-(Aminomethyl)anilineHCID 181649HOAtHCID 710621452-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid2×

Product 1

HCID 86718893N3-(2-Aminobenzyl)-4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-N1-(naphthalen-2-ylsulfonyl)isophthalamideYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid (Intermediate 91F, 50 mg, 0.080 mmol) in CH2Cl2 (1.1 mL) and DMF (0.2 mL) was added 2-(aminomethyl)aniline (20 mg, 0.16 mmol) followed by EDC (34 mg, 0.18 mmol) and 1-hydroxy-7-azabenzo-triazole (290 μL, 0.18 mmol, 0.6M solution in DMF). The resulting reaction mixture was stirred at room temperature overnight, then quenched with sat. aq. NH4Cl solution and extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (gradient from 0% to 10% MeOH/CH2Cl2) provided the title compound (35 mg, 60%) as a pale yellow, oily solid. MS(ESI+) m/z 729.2 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. customquenched with sat. aq. NH4Cl solution
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography (gradient from 0% to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b85120b236384e1394d1805b4b2fdfe9
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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