Diisopropylethylamine → HCID 22890448, compound

HRID 993140Notes

Reaction equation

HRID 993140 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]([C:23]2[CH:28]=[C:27]([O:29][CH2:30][CH3:31])[C:26]([O:32][CH2:33][CH3:34])=[CH:25][C:24]=2[N:35]([S:37]([CH3:40])(=[O:39])=[O:38])[CH3:36])[C:11]([NH:13][S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:16])=[O:15])=[O:12])=[CH:5][CH:4]=1)#[N:2].C([N:44](C(C)C)CC)(C)C.Cl.NO>C(O)C.CO.C(O)(=O)C.[Ni]>[C:17]1([S:14]([NH:13][C:11](=[O:12])[CH:10]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([C:1]([NH2:44])=[NH:2])=[CH:4][CH:5]=2)[C:23]2[CH:28]=[C:27]([O:29][CH2:30][CH3:31])[C:26]([O:32][CH2:33][CH3:34])=[CH:25][C:24]=2[N:35]([S:37]([CH3:40])(=[O:38])=[O:39])[CH3:36])(=[O:16])=[O:15])[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

8

Reactant 3

HCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochlorideHCID 22351234HCID 22351234, compound

Product 1

HCID 22890448HCID 22890448, compound

Reagents, catalysts & solvents 4

HCID 935NickelCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

The N-{(4-cyanophenylamino)-[4,5-diethoxy-2-(methanesulfonyl-methyl-amino)-phenyl]-acetyl}benzenesulfonamide obtained above (126 mg, 0.21 mmole) was dissolved in ethanol (1.8 ml) and heated to 60° C. Diisopropylethylamine (DIPEA—260 ul, 1.5 mmole) was added followed by hydroxylamine-hydrochloride (74 mg, 1.04 mmole). The reaction was stirred at 60° C. under a nitrogen atmosphere for 6 hours. The reaction was then allowed to cool to room temperature. The solution was diluted with methanol (5 ml) and acetic acid (2 ml) and Raney Nickel 2800 (ca. 50 mg) added as a suspension. The reaction was then stirred vigorously under a hydrogen atmosphere for 1 hour. The catalyst was filtered off and the solvent removed. The crude product was purified by preparative reverse-phase HPLC using a water-acetonitrile (0.1% TFA) gradient to yield 40 mg of desired 4-{2-benzenesulfonylamino-1-[4,5-diethoxy-2-(methanesulfonyl-methyl-amino)phenyl]-2-oxo-ethylamino}benzamidine as its trifluoroacetic acid salt. MS: (M+H)=604.

Workup

  1. temperatureto cool to room temperature
  2. additionadded as a suspension
  3. stirringThe reaction was then stirred vigorously under a hydrogen atmosphere for 1 hour
  4. filtrationThe catalyst was filtered off
  5. customthe solvent removed
  6. customThe crude product was purified by preparative reverse-phase

Sources & evidence

ORD record
ord-f545947768c441f9a6c67ef53237e7f7
Source dataset
uspto-grants-2002_10
Patent number
US06472393B1

Reaction notes

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