1-Hydroxybenzotriazole → HCID 11202234, compound

HRID 1270994Notes

Reaction equation

HRID 1270994 reaction equation
C(N(CC)CCN[C:7](=[O:34])/[CH:8]=[CH:9]/[C@@H:10]([NH:18][C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:24][CH:23]=1)=[O:20])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)C.[CH:37]([NH:40][CH2:41][CH2:42][NH2:43])([CH3:39])[CH3:38].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[CH:37]([NH:40][CH2:41][CH2:42][NH:43][C:7](=[O:34])/[CH:8]=[CH:9]/[C@@H:10]([NH:18][C:19]([NH:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:26][CH:27]=1)=[O:20])[CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)([CH3:39])[CH3:38]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 88098N-IsopropylethylenediamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11409113HCID 11409113, compound

Product 1

HCID 11202234HCID 11202234, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (E)-(S)-4-(3-biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (Example 19, step A) (0.30 g, 0.78 mmol), N-isopropyl-ethane-1,2-diamine (0.087 g, 0.85 mmol) and HOBt (0.16 g, 1.16 mmol) in DMF (7.8 mL), was added EDCl (0.22 g, 1.16 mmol). The resulting solution was stirred under N2 at rt for 20 h. The solution was diluted with H2O (50 mL) and extracted with 3:1 EtOAc/iPrOH (3×60 mL). The combined organic extracts were washed with 1 N NaOH (1×50 mL) and brine (75 mL), dried (Na2SO4) and filtered, and the solvent was removed. The residue was purified by column chromatography on silica gel using a gradient of 2–10% (MeOH (1% NH4OH)/CH2Cl2 to afford 0.18 g (51%) of the desired product as a white solid. Rf=0.26 (10% MeOH (1% NH4OH)/CH2Cl2). MS (electrospray): mass calculated for C29H34N4O2, 470.27; m/z found, 471.3 [M+H]+, 493.2 [M+Na]+, 941.5 [2M+H]+. 1H NMR (400 MHz, CDCl3): 8.10 (s, 1H), 7.48 (d, J=7.5 Hz, 2H), 7.43 (d, J=8.5 Hz, 2H), 7.39–7.33 (m, 5H), 7.31–7.25 (m, 3H), 7.21 (d, J=7.24 Hz, 2H), 6.76 (dd, J=15.3, 5.7 Hz, 1H), 6.25 (d, J=8.3 Hz, 1H), 6.00 (d, J=15.3 Hz, 1H), 4.86–4.79 (m, 1H), 3.46–3.41 (m, 1H), 3.31–3.27 (m, 1H), 2.95–2.85 (m, 2H), 2.77–2.67 (m, 3H), 1.01 (d, J=6.0 Hz, 6H).

Workup

  1. extractionextracted with 3:1 EtOAc/iPrOH (3×60 mL)
  2. washThe combined organic extracts were washed with 1 N NaOH (1×50 mL) and brine (75 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent was removed
  6. customThe residue was purified by column chromatography on silica gel using a gradient of 2–10% (MeOH (1% NH4OH)/CH2Cl2

Sources & evidence

ORD record
ord-3c78493126c5474790275c634dfc5c73
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

Loading…