Triethylamine → HCID 58102037, compound

HRID 41714Notes

Reaction equation

HRID 41714 reaction equation
[C:1]([N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:12]=[N: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)=[CH:15][CH:16]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(Cl)(O[C:38](=[O:44])OC(Cl)(Cl)Cl)Cl.C(N(C(C)C)CC)(C)C.Cl.[NH2:56][CH:57]1[CH:64]2[CH2:65][C:60]3([C:67]([NH2:69])=[O:68])[CH2:61][CH:62]([CH2:66][CH:58]1[CH2:59]3)[CH2:63]2>ClCCl.O.CN(C=O)C>[C:67]([C:60]12[CH2:59][CH:58]3[CH2:66][CH:62]([CH2:63][CH:64]([CH:57]3[NH:56][C:38]([N:20]3[C:21]4[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=4)[N:17]([C:14]4[N:13]=[CH:12][C:11]([CH:8]5[CH2:9][CH2:10][N:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH2:6][CH2:7]5)=[CH:16][CH:15]=4)[CH2:18][CH2:19]3)=[O:44])[CH2:65]1)[CH2:61]2)(=[O:68])[NH2:69]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 66863440HCID 66863440, compoundHCID 66863860HCID 66863860, compound

Product 1

HCID 58102037HCID 58102037, compoundYield 112.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-(1′-(tert-Butyl)-1′,2′,3′,4′,5′,6′-hexahydro-3,4′-bipyridinyl-6-yl)-1,2,3,4-tetra-hydroquinoxaline (0.12 g, 0.35 mmol) is placed in 3.5 ml of dichloromethane at 0° C. Triethylamine (0.10 ml, 0.7 mmol) and then triphosgene (0.041 g, 0.14 mmol) are added. The reaction medium is stirred at ambient temperature for 3 h. 3.5 ml of DMF, diisopropylethylamine (0.15 ml, 0.87 mmol) and then 4-aminoadamantane-1-carboxylic acid amide hydrochloride (0.08 g, 0.35 mmol) are then added. The reaction medium is heated at 50° C. for 18 h under nitrogen. After hydrolysing on 40 ml of H2O and extracting 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). 0.09 g of 4-(1′-(tert-butyl)-1′,2′,3′,4′,5′,6′-hexahydro-3,4′-bipyridinyl-6-yl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid (5-carbamoyladamantan-2-yl)amide is obtained and is 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. extractionextracting with ethyl acetate
  3. washthe organic phase is washed with water
  4. dry with materialwith a saturated aqueous sodium chloride solution, dried over MgSO4
  5. concentrationconcentrated to dryness
  6. customThe crude product obtained
  7. customis chromatographed on silica gel, elution

Sources & evidence

ORD record
ord-9138e17ee7974c6fb3d0d2c5365db837
Source dataset
uspto-grants-2013_09
Patent number
US08530657B2

Reaction notes

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