1-Hydroxybenzotriazole → N-{4-[(4-butylphenyl)ethynyl]benzyl}-N-hexyl-2,2-dimethyl-4-oxo-4H-1,3-benzodioxine-6-carboxamide

HRID 551919Notes

Reaction equation

HRID 551919 reaction equation
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:26]=[CH:25][C:16]([CH2:17][NH:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[CH3:27][C:28]1([CH3:42])[O:33][C:32]2[CH:34]=[CH:35][C:36]([C:38]([OH:40])=O)=[CH:37][C:31]=2[C:30](=[O:41])[O:29]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:26]=[CH:25][C:16]([CH2:17][N:18]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:38]([C:36]3[CH:35]=[CH:34][C:32]4[O:33][C:28]([CH3:27])([CH3:42])[O:29][C:30](=[O:41])[C:31]=4[CH:37]=3)=[O:40])=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57554478N-{4-[(4-butylphenyl)ethynyl]benzyl)-1-hexanamineHCID 575544892,2-dimethyl-4-oxo-4H-1,3-benzodioxine-6-carboxylic acid

Product 1

HCID 11519643N-{4-[(4-butylphenyl)ethynyl]benzyl}-N-hexyl-2,2-dimethyl-4-oxo-4H-1,3-benzodioxine-6-carboxamideYield 47.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of N-{4-[(4-butylphenyl)ethynyl]benzyl}-1-hexanamine (144 mg, 0.41 mmol), 2,2-dimethyl-4-oxo-4H-1,3-benzodioxine-6-carboxylic acid (92 mg, 0.41 mmol), EDC.HCl (87 mg, 0.46 mmol), HOBT (61 mg, 0.46 mmol) and DIEA (105 μL, 0.62 mmol) in DCM (10 mL) was stirred at rt overnight. Then the reaction mixture was diluted with DCM and washed with a saturated aqueous solution of NaHCO3, a saturated aqueous solution of NH4Cl and brine. The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography on silicagel (EtOAc/c-Hex (20/80)) to give 108 mg (47%) of the title compound as a colorless oil. HPLC, Rt: 6.14 min (purity: 99.9%). 1H NMR (CD3Cl3) δ: 0.82 (m, 3H), 0.91 (t, J=7.3 Hz, 3H), 1.32-1.40 (m, 10H), 1.57 (m, 2H), 1.72 (s, 6H), 2.59 (t, J=7.6 Hz, 2H), 3.16-3.41 (m, 2H), 4.40-4.72 (m, 2H), 7.00 (m, 2H), 7.14 (d, J=8.3 Hz, 2H), 7.25 (m, 1H), 7.42 (d, J=8.1 Hz, 2H), 7.48 (d, J=8.1 Hz, 2H), 7.61 (m, 1H), 8.03 (s, 1H).

Workup

  1. washwashed with a saturated aqueous solution of NaHCO3
  2. dry with materialThe organic layer was dried over MgSO4
  3. customthe solvent was removed under reduced pressure
  4. customThe crude product was purified by flash chromatography on silicagel (EtOAc/c-Hex (20/80))

Sources & evidence

ORD record
ord-37344fc2cf46452fabc7b643cd9a6880
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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