Triethylamine → 1-Acryloyl-4-(2-((2',5',6-trichloro-4-methoxy-[1,1'-biphenyl]-3-yl)amino)acetyl)piperazine-2-carboxamide

HRID 588823Notes

Reaction equation

HRID 588823 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]1[C:14]([Cl:15])=[CH:13][C:12]([O:16][CH3:17])=[C:11]([NH:18][CH2:19][C:20]([OH:22])=O)[CH:10]=1.CCN(CC)CC.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.Cl.[C:53]([N:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH:58]1[C:63]([NH2:65])=[O:64])(=[O:56])[CH:54]=[CH2:55]>CN(C=O)C>[C:53]([N:57]1[CH2:62][CH2:61][N:60]([C:20](=[O:22])[CH2:19][NH:18][C:11]2[CH:10]=[C:9]([C:3]3[CH:4]=[C:5]([Cl:8])[CH:6]=[CH:7][C:2]=3[Cl:1])[C:14]([Cl:15])=[CH:13][C:12]=2[O:16][CH3:17])[CH2:59][CH:58]1[C:63]([NH2:65])=[O:64])(=[O:56])[CH:54]=[CH2:55]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 90455762Glycine, N-(2',5',6-trichloro-4-methoxy[1,1'-biphenyl]-3-yl)-HCID 904602351-Acryloylpiperazine-2-carboxamide hydrochloride

Product 1

HCID 1176109311-Acryloyl-4-(2-((2',5',6-trichloro-4-methoxy-[1,1'-biphenyl]-3-yl)amino)acetyl)piperazine-2-carboxamideYield 3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2-((2′,5′,6-Trichloro-4-methoxy-[1,1′-biphenyl]-3-yl)amino)acetic acid (231 mg, 0.641 mmol) and Et3N (592 mg, 2.564 mmol) in DMF (3 mL) at 0° C., EDCI.HCl (184 mg, 0.961 mmol) and HOBt (134 mg, 0.961 mmol) were added and the resulting mixture was stirred at 0° C. for 30 min. To this mixture, the above 1-acryloylpiperazine-2-carboxamide hydrochloride (160 mg) was added and stirred at room temperature for 16 h. The 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=30:1) to afford the desired product (10 mg, 2.97% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 7.60-7.38 (m, 3H), 6.70-6.99 (m, 1H), 6.86-6.78 (m, 1H), 6.54-6.49 (m, 1H), 6.16-6.10 (m, 1H), 5.76-5.69 (m, 1H), 5.32-5.31 (m, 1H), 4.93-4.84 (m, 1H), 4.93-4.84 (m, 1H), 4.70-4.62 (m, 1H), 4.35-4.32 (m, 1H), 4.04-3.96 (m, 2H), 3.89-3.63 (m, 1H), 2.90-2.86 (m, 1H). ESI-MS m/z: 525.2[M+H]+.

Workup

  1. stirringstirred at room temperature for 16 h
  2. customThe 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=30:1)

Sources & evidence

ORD record
ord-0eb43539e645439cab49ec1ebd22ed0b
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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