1-Hydroxybenzotriazole → 4-[(4-butylphenyl)ethynyl]-N-[(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)methyl]-N-hexylbenzamide

HRID 551926Notes

Reaction equation

HRID 551926 reaction equation
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH2:53]([NH:59][CH2:60][C:61]1[CH:73]=[CH:72][C:64]2[O:65][C:66]([CH3:71])([CH3:70])[O:67][C:68](=[O:69])[C:63]=2[CH:62]=1)[CH2:54][CH2:55][CH2:56][CH2:57][CH3:58]>C(Cl)Cl>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][C:16]([C:17]([N:59]([CH2:60][C:61]3[CH:73]=[CH:72][C:64]4[O:65][C:66]([CH3:71])([CH3:70])[O:67][C:68](=[O:69])[C:63]=4[CH:62]=3)[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])=[O:19])=[CH:20][CH:21]=2)=[CH:9][CH:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219465344-(4-Butylphenylethynyl)benzoic acidHCID 575545526-[(hexylamino)methyl]-2,2-dimethyl-4H-1,3-benzodioxin-4-one

Product 1

HCID 116209514-[(4-butylphenyl)ethynyl]-N-[(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)methyl]-N-hexylbenzamideYield 75.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 4-(4-butylphenylethynyl)benzoic acid (330 mg, 1.19 mmol), EDC.HCl (231 mg, 1.21 mmol), HOBT (163 mg, 1.21 mmol) and DIEA (256 μl, 1.51 mmol) in DCM (15 mL) was stirred 10 min at rt. Then a solution of 6-[(hexylamino)methyl]-2,2-dimethyl-4H-1,3-benzodioxin-4-one (293 mg, 1.01 mmol) in DCM (5 mL) was added and the resulting mixture was stirred 3 hrs at rt. The reaction mixture was diluted with DCM and washed with a saturated aqueous solution of NaHCO3, an aqueous solution of HCl (1N) and brine. Organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. Purification by flash chromatography on silica gel (EtOAc/c-Hex (20/80)) gave 420 mg (73%) of the title compound. HPLC, Rt: 6.18 min (purity: 92.3%). A second purification by preparative HPLC with a X-Terra column allowed the isolation of the title compound (300 mg, 54% yield) as a white powder. HPLC, Rt: 6.15 min (purity: 99.1%). LC/MS, M+(ESI): 552.7. 1H NMR (CDCl3) δ: 0.82 (m, 3H), 0.91 (t, J=7.3 Hz, 3H), 1.09-1.41 (m, 8H), 1.53 (m, 4H), 1.72 (s, 6H), 2.60 (t, J=7.6 Hz, 2H), 3.16-3.45 (m, 2H), 4.50-4.70 (m, 2H), 6.96 (d, J=8.5 Hz, 1H), 7.15 (d, J=8.1 Hz, 2H), 7.37 (d, J=8.3 Hz, 2H), 7.42 (d, J=7.9 Hz, 2H), 7.52-7.84 (m, 4H).

Workup

  1. washwashed with a saturated aqueous solution of NaHCO3
  2. dry with materialOrganic layer was dried over MgSO4
  3. customthe solvent was removed under reduced pressure
  4. customPurification by flash chromatography on silica gel (EtOAc/c-Hex (20/80))

Sources & evidence

ORD record
ord-c62855f58f5040f0abc7019a6f8dc867
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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