Nitrogen → {2'-[3-(3,4,5-Trimethoxy-phenyl)-propionylamino]-biphenyl-3-yl}-acetic acid methyl ester

HRID 1944262

Reaction equation

HRID 1944262 reaction equation
N#N.CCN=C=NCCCN(C)C.Cl.CCN(CC)CC.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH2:34][CH2:35][C:36]([OH:38])=O)[CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31].[CH3:39][O:40][C:41](=[O:56])[CH2:42][C:43]1[CH:44]=[C:45]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[NH2:55])[CH:46]=[CH:47][CH:48]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:39][O:40][C:41](=[O:56])[CH2:42][C:43]1[CH:44]=[C:45]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[NH:55][C:36](=[O:38])[CH2:35][CH2:34][C:26]2[CH:27]=[C:28]([O:32][CH3:33])[C:29]([O:30][CH3:31])=[C:24]([O:23][CH3:22])[CH:25]=2)[CH:46]=[CH:47][CH:48]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 8471TriethylamineHCID 648603,4,5-Trimethoxyhydrocinnamic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16116037(2'-Amino-biphenyl-3-yl)-acetic acid methyl ester

Product 1

HCID 16116560{2'-[3-(3,4,5-Trimethoxy-phenyl)-propionylamino]-biphenyl-3-yl}-acetic acid methyl esterYield 48%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(The following reaction is done in an anhydrous N2 atmosphere.) Suspend EDC HCl (61 mg, 0.32 mmol) and Et3N (44 μL, 0.32 mmol) in anhydrous DCM (1.0 mL) and stir the resulting solution for 5 min at rt. Add 3-(3,4,5-Trimethoxy-phenyl)-propionic acid (55 mg, 0.23 mmol) and DMAP (2 mg, 0.02 mmol) and stir the resulting solution for 15 min. Add (2′-Amino-biphenyl-3-yl)-acetic acid methyl ester (49) (50 mg, 0.21 mmol) and stir the reaction solution overnight at rt. Quench reaction solution with water, separate layers and extract aqu. layer with DCM (3 times). Wash combined organic layer with brine and dry with Na2SO4. Purify the crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+1) to obtain {2′-[3-(3,4,5-Trimethoxy-phenyl)-propionylamino]-biphenyl-3-yl}-acetic acid methyl ester (50) (46 mg, 48%) as a yellow oil. 1H NMR (400 MHz, CDCl3): 2.50 (t, 2H, J=7.6 Hz); 2.90 (t, 2H, J=7.7 Hz); 3.64 (s, 2H); 3.65 (s, 3H); 3.77 (s, 6H); 3.78 (s, 3H); 6.38 (s, 2H); 7.09-7.18 (m, 3H); 7.19-7.28 (m, 3H); 7.34 (d, 1H, J=8.1 Hz); 7.38 (d, 1H, J=7.8 Hz); 8.31 (br.d, 1H, J=7.8 Hz).

Workup

  1. custom(The following reaction
  2. customQuench
  3. customreaction solution with water
  4. customseparate layers
  5. extractionextract aqu
  6. washWash
  7. dry with materialdry with Na2SO4
  8. customPurify the crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+1)

Sources & evidence

ORD record
ord-63a8547a89bb4010a67109a599643442
Source dataset
uspto-grants-2013_03
Patent number
US08394835B2

Linked notes

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