Sodium Hydroxide → Methyl 5-{[{4-[(4-butylphenyl)ethynyl]benzoyl}(hexyl)amino]methyl}-2-fluorobenzoate

HRID 551989Notes

Reaction equation

HRID 551989 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].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C.[F:53][C:54]1[CH:63]=[CH:62][C:61]([CH2:64][NH:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH3:71])=[CH:60][C:55]=1[C:56]([O:58][CH3:59])=[O:57].[OH-].[Na+]>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:65]([CH2:64][C:61]3[CH:62]=[CH:63][C:54]([F:53])=[C:55]([CH:60]=3)[C:56]([O:58][CH3:59])=[O:57])[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH3:71])=[O:19])=[CH:20][CH:21]=2)=[CH:9][CH:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 6

HCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219465344-(4-Butylphenylethynyl)benzoic acidHCID 57554492Methyl 2-fluoro-5-[(hexylamino)methyl]benzoate

Product 1

HCID 57554527Methyl 5-{[{4-[(4-butylphenyl)ethynyl]benzoyl}(hexyl)amino]methyl}-2-fluorobenzoateYield 59.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution of 4-(4-butylphenylethynyl)benzoic acid (312 mg; 1.12 mmol) in DCM (15 mL) were added HOBT (181 mg; 1.35 mmol), EDC-HCl (258 mg; 1.35 mmol) and DIEA (362 mg; 2.81 mmol). The mixture was stirred for 10 min at room temperature under N2 atmosphere before the addition of methyl 2-fluoro-5-[(hexylamino)methyl]benzoate (300 mg; 1.12 mmol). The reaction mixture was then stirred at 25° C. under N2 atmosphere overnight. It was diluted in DCM (100 mL) and poured into NaOH (1N, 75 mL). The organic layer was washed with brine (100 mL), dried over magnesium sulfate, filtrated and the solvent was removed under reduced pressure. Purification by flash chromatography using silicagel (c-Hex/EtOAc, gradient from 9:1 to 1:1) gave 350 mg (59%) of the title compound as a white powder. HPLC, Rt: 6.19 min (purity=99.7%). LC/MS, M+(ESI): 528.3. 1H NMR (CDCl3) δ: 7.91 (m, 1H), 7.55 (m, 3H), 7.41 (m, 4H), 7.15 (m, 3H), 4.72 (m, 1H), 4.50 (m, 1H), 3.93 (s, 3H), 3.42 (m, 1H), 3.15 (m, 1H), 2.61 (t, J=5.5 Hz, 2H), 1.59 (qt, J=7.7 Hz, 2H), 1.2 (m, 10H), 0.92 (t, J=7.3 Hz, 3H), 0.8 (m, 3H).

Workup

  1. washThe organic layer was washed with brine (100 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltrated
  4. customthe solvent was removed under reduced pressure
  5. customPurification by flash chromatography

Sources & evidence

ORD record
ord-37dc80697b1a42b29853573750ffbef8
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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