Diisopropylamine → 4-[5-(4-isobutyl piperazin-1-yl)pyridin-2-yl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid (5-carbamoyladamantan-2-yl)amide

HRID 41711Notes

Reaction equation

HRID 41711 reaction equation
[CH2:1]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:12]=[CH:13][C:14]([N:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[NH:20][CH2:19][CH2:18]3)=[N:15][CH:16]=2)[CH2:7][CH2:6]1)[CH:2]([CH3:4])[CH3:3].C(N(CC)CC)C.ClC(Cl)(O[C:38](=[O:44])OC(Cl)(Cl)Cl)Cl.C(NC(C)C)(C)C.[NH2:53][CH:54]1[CH:61]2[CH2:62][C:57]3([C:64]([NH2:66])=[O:65])[CH2:58][CH:59]([CH2:63][CH:55]1[CH2:56]3)[CH2:60]2>ClCCl.CN(C=O)C>[C:64]([C:57]12[CH2:56][CH:55]3[CH2:63][CH:59]([CH2:60][CH:61]([CH:54]3[NH:53][C:38]([N:20]3[C:21]4[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=4)[N:17]([C:14]4[CH:13]=[CH:12][C:11]([N:8]5[CH2:9][CH2:10][N:5]([CH2:1][CH:2]([CH3:4])[CH3:3])[CH2:6][CH2:7]5)=[CH:16][N:15]=4)[CH2:18][CH2:19]3)=[O:44])[CH2:62]1)[CH2:58]2)(=[O:65])[NH2:66]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 8471TriethylamineHCID 94429TriphosgeneHCID 668630161-[5-(4-Isobutylpiperazin-1-yl)pyridin-2-yl]-1,2,3,4-tetrahydroquinoxalineHCID 668634414-Aminoadamantane-1-carboxamide

Product 1

HCID 581020504-[5-(4-isobutyl piperazin-1-yl)pyridin-2-yl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid (5-carbamoyladamantan-2-yl)amideYield 147.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-[5-(4-Isobutylpiperazin-1-yl)pyridin-2-yl]-1,2,3,4-tetrahydroquinoxaline (0.25 g, 0.71 mmol) is placed in 7 ml of dichloromethane at 0° C. under nitrogen. Triethylamine (0.2 ml, 1.43 mmol) and then triphosgene (0.084 g, 0.28 mmol) are added. The reaction medium is stirred at ambient temperature for 3 h. 7.1 ml of DMF, diisopropylamine (0.31 ml, 1.78 mmol) and then 4-aminoadamantane-1-carboxylic acid amide (0.164 g, 0.71 mmol) are then added. The reaction medium is heated at 50° C. for 18 h under nitrogen. After hydrolysis on 50 ml of ice and extraction with ethyl acetate, the organic phase is washed with water and then with a saturated aqueous sodium chloride solution, dried over MgSO4 and concentrated to dryness. The crude product obtained is chromatographed on silica gel, elution being carried out with an ethyl acetate/methanol/aqueous ammonia gradient in dichloromethane varying from 100/0/0/0 to 7/2.5/0.5/0.5 (dichloromethane/ethyl acetate/methanol/aqueous ammonia). 0.236 g of 4-[5-(4-isobutyl piperazin-1-yl)pyridin-2-yl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid (5-carbamoyladamantan-2-yl)amide is obtained, subsequently triturated from diethyl ether. The crystals obtained are filtered off and dried.

Workup

  1. temperatureThe reaction medium is heated at 50° C. for 18 h under nitrogen
  2. customAfter hydrolysis
  3. extractionon 50 ml of ice and extraction with ethyl acetate
  4. washthe organic phase is washed with water
  5. dry with materialwith a saturated aqueous sodium chloride solution, dried over MgSO4
  6. concentrationconcentrated to dryness
  7. customThe crude product obtained
  8. customis chromatographed on silica gel, elution

Sources & evidence

ORD record
ord-368b19a6a628420f9384aee5d453a383
Source dataset
uspto-grants-2013_09
Patent number
US08530657B2

Reaction notes

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