Water → HCID 44570931, compound

HRID 416223Notes

Reaction equation

HRID 416223 reaction equation
[N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH2:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([OH:30])=O)=[CH:26][CH:25]=4)[N:17]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:33]1([NH2:40])[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[NH2:39].CCN(CC)CC.C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.Cl>C(#N)C>[NH2:39][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[NH:40][C:28](=[O:30])[C:27]1[CH:31]=[CH:32][C:24]([CH2:23][NH:22][C:18]2[N:17]=[C:16]([C:13]3[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)=[CH:11][CH:12]=3)[CH:21]=[CH:20][N:19]=2)=[CH:25][CH:26]=1

Participants

8

Reactant 6

HCID 962WaterHCID 7243O-PhenylenediamineHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58930425HCID 58930425, compound

Product 1

HCID 44570931HCID 44570931, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 21 (crude from the previous step) in dry acetonitrile (50 mL) was added 1,2-phenylenediamine (1.83 g, 16.9 mmol) followed by Et3N (2.65 mL, 19.0 mmol), HOBt.H2O (1.03 g, 7.6 mmol) and EDCI.HCl (1.62 g, 8.5 mmol). The mixture was stirred at room temperature for 72 h, filtered to remove salts and filtrate was concentrated to form a residue, which was purified by flash chromatography on silica gel (MeOH/CH2Cl2: 2/98 to 5/95). Trituration of this material with a mixture of EtOAc/CH2Cl2, allowed affording the title compound 22a (696 mg, 1.3 mmol, 31% yield over 2 steps) as a white solid. 1H NMR: (400 MHz, DMSO-d6) δ (ppm): 9.55 (s, 1H), 8.25 (d, J=5.2 Hz, 1H), 8.00 (d, J=8.4 Hz, 2H), 7.88 (d, J=8.4 Hz, 2H), 7.77 (t, J=6.4 Hz, 1H), 7.44 (d, J=7.2 Hz, 2H), 7.11 (d, J=7.6 Hz, 1H), 7.07 (d, J=5.2 Hz, 1H), 7.01 (d, J=8.4 Hz, 2H), 6.92 (td, J=7.6, 1.6 Hz, 1H), 6.73 (dd, J=8.0, 1.6 Hz, 1H), 6.55 (td, J=7.4, 1.2 Hz, 1H), 4.85 (s, 2H), 4.61 (d, J=5.6 Hz, 2H), 4.13 (t, J=5.6 Hz, 2H), 3.55 (t, J=4.4 Hz, 4H), 2.68 (t, J=5.6 Hz, 2H), 2.45 (t, J=4.4 Hz, 4H).

Workup

  1. filtrationfiltered
  2. customto remove salts and filtrate
  3. concentrationwas concentrated
  4. customto form a residue, which
  5. customwas purified by flash chromatography on silica gel (MeOH/CH2Cl2: 2/98 to 5/95)
  6. additionTrituration of this material with a mixture of EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-cebf1e0072734ff893dbca7f282e23d0
Source dataset
uspto-grants-2012_01
Patent number
US08088805B2

Reaction notes

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