Triethylamine → HCID 67050667, compound

HRID 886148Notes

Reaction equation

HRID 886148 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH:14]([N:17]1[C:21]([N:22]2[N:31]=[C:30]3[C:24]([CH2:25][CH2:26][O:27][C:28]4[CH:35]=[CH:34][C:33]([C:36](O)=[O:37])=[CH:32][C:29]=43)=[CH:23]2)=[N:20][CH:19]=[N:18]1)([CH3:16])[CH3:15].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][N:11]([C:36]([C:33]2[CH:34]=[CH:35][C:28]3[O:27][CH2:26][CH2:25][C:24]4[C:30](=[N:31][N:22]([C:21]5[N:17]([CH:14]([CH3:15])[CH3:16])[N:18]=[CH:19][N:20]=5)[CH:23]=4)[C:29]=3[CH:32]=2)=[O:37])[CH2:12][CH2:13]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 67050628HCID 67050628, compound

Product 1

HCID 67050667HCID 67050667, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-Boc piperazine (101 mg, 0.54 mmol), 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-2H-6-oxa-1,2-diaza-benzo[e]azulene-9-carboxylic acid (180 mg, 0.53 mmol), EDCI (151 mg, 0.79 mmol), HOBt (107 mg, 0.795 mmol) and triethylamine (216 μL, 1.54 mmol) in DMF (2 mL) was stirred at RT for 20 h. The mixture was diluted with ethyl acetate and washed (water, saturated aqueous sodium hydrogen carbonate and then brine), dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% MeOH in DCM) to give 4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-2H-6-oxa-1,2-diaza-benzo[e]azulene-9-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester (258 mg, 96%). The intermediate carboxylic acid tert-butyl ester was dissolved in DCM (20 mL) and treated with 4N HCl in dioxane (4 mL) and stirred for 3 h at RT before adding diethyl ether (20 mL). The resultant precipitate was collected by filtration and washed with diethyl ether to give 145 as a white solid (209 mg, 93%). 1H NMR (400 MHz, DMSO-d): δ 9.32 (s, 2H); 8.37 (s, 1H); 8.31 (d, J=2.20 Hz, 1H); 8.06 (s, 1H); 7.44 (dd, J=8.37, 2.21 Hz, 1H); 7.15 (d, J=8.37 Hz, 1H); 5.32-5.23 (m, 1H); 4.37 (t, J=4.98 Hz, 2H); 3.77 (s, 4H); 3.15 (t, J=6.94 Hz, 6H); 1.51 (d, J=6.59 Hz, 6H). LCMS: RT=6.02 min, M+H+=408

Workup

  1. washwashed (water, saturated aqueous sodium hydrogen carbonate
  2. dry with materialbrine), dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-654210e335b344feb443120c12cfecfc
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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