Triethylamine → HCID 90462777, compound

HRID 588806Notes

Reaction equation

HRID 588806 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]([Cl:14])=[CH:12][C:11]([CH2:15][CH3:16])=[C:10]([NH:17][CH2:18][C:19]([OH:21])=O)[CH:9]=1.[CH3:22][CH2:23]N(CC)CC.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[N:51]1([C:57]([O:59]C(C)(C)C)=O)[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]([Cl:14])=[CH:12][C:11]([CH2:15][CH3:16])=[C:10]([NH:17][CH2:18][C:19]([N:54]2[CH2:53][CH2:52][N:51]([C:57](=[O:59])[CH:22]=[CH2:23])[CH2:56][CH2:55]2)=[O:21])[CH:9]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 90455874HCID 90455874, compound

Product 1

HCID 90462777HCID 90462777, compoundYield 21.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2-((2′,6-dichloro-4-ethyl-[1,1′-biphenyl]-3-yl)amino)acetic acid (150 mg, 0.466 mmol) and Et3N (235 mg, 2.33 mmol) in DMF (5 mL) at 0° C., EDCI.HCl (178 mg, 0.932 mmol) and HOBt (126 mg, 0.932 mmol) were added and the resulting mixture was stirred at 0° C. for 30 min. To this mixture, tert-butyl piperazine-1-carboxylate (123 mg, 0.698 mmol) was added and then stirred at room temperature for 16 h. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (DCM/MeOH=50:1) to afford the desired product (45 mg, 21.7% yield). 1H NMR (400 MHz, DMSO-d6) δ: 7.56-7.54 (m, 1H), 7.43-7.41 (m, 2H), 7.32-7.30 (m, 1H), 7.14 (s, 1H), 6.81 (dd, J=10.4, 16.4 Hz, 1H), 6.54 (s, 1H), 6.13 (dd, J=2.4, 16.8 Hz, 1H), 5.71 (dd, J=2.0, 10.4 Hz, 1H), 5.25 (bs., 1H), 3.96 (d, J=4.4 Hz, 2H), 3.56-3.52 (m, 8H), 2.54 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H). ESI-MS m/z: 444.3 [M−H]−.

Workup

  1. stirringstirred at room temperature for 16 h
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel (DCM/MeOH=50:1)

Sources & evidence

ORD record
ord-bf78b75f5fa94b7caa12de194270f287
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

Loading…