Triethylamine → N-[[4-[[[Cyclobutyl[2-(2,3-dichlorophenyl)-2-hydroxyethyl]amino]carbonyl]amino]phenyl]methyl]-2,2-dimethylpropanamide

HRID 1057983Notes

Reaction equation

HRID 1057983 reaction equation
[CH:1]1([NH:5][CH2:6][CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[C:10]=2[Cl:16])[OH:8])[CH2:4][CH2:3][CH2:2]1.[N:17]([C:20]1[CH:33]=[CH:32][C:23]([CH2:24][NH:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:22][CH:21]=1)=[C:18]=[O:19].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:16][C:10]1[C:11]([Cl:15])=[CH:12][CH:13]=[CH:14][C:9]=1[CH:7]([OH:8])[CH2:6][N:5]([CH:1]1[CH2:4][CH2:3][CH2:2]1)[C:18](=[O:19])[NH:17][C:20]1[CH:21]=[CH:22][C:23]([CH2:24][NH:25][C:26](=[O:31])[C:27]([CH3:29])([CH3:30])[CH3:28])=[CH:32][CH:33]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 18672517HCID 18672517, compoundHCID 18672521N-(4-isocyanato-benzyl)-2,2-dimethyl-propionamide

Product 1

HCID 10184984N-[[4-[[[Cyclobutyl[2-(2,3-dichlorophenyl)-2-hydroxyethyl]amino]carbonyl]amino]phenyl]methyl]-2,2-dimethylpropanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a test tube containing 0.3 mmol 2-cyclobutylamino-1-(2,3-dichlorophenyl)ethanol in 1 ml CH2Cl2 was added 314 μl of a 0.1 M solution of N-(4-isocyanato-benzyl)-2,2-dimethyl-propionamide and 0.43 μl triethylamine. The solution was allowed to stand for 1.5 h, then saturated sodium bicarbonate (1 ml) was added and the resulting mixture extracted with 1 mL EtOAc. The EtOAc extract was washed with water (2×1 ml), and the solvent removed by vacuum centrifugation over 48 h. The resulting solid was dissolved in 450 ml DMF and purified by reverse phase preparatory HPLC (Zorbax 2.5×7 cm C8 column, linear gradient 5-100% CH3CH/H2O (0.1% TFA), 15 mL/Min). The desired fractions were combined and the solvent removed by vacuum centrifugation to give. The desired fractions were combined and placed on a speed vacuum overnight for 15 h to give N-(4-{3-[2-(2,3-Dichloro-phenyl)-2-hydroxy-ethyl]-3-cyclobutyl-ureido}-benzyl)-2,2-dimethyl-propionamide. 1H NMR δH (CD3OD) 7.67-7.66 (d, 1H, J 1.22 Hz), 7.64-7.63 (d, 1H, J 1.23 Hz), 7.38-7.36 (t, 1H, J 7.94 Hz), 7.28-7.25 (d, 2H, J 8.55 Hz), 7.20-7.17 (d, 2H, J 8.24 Hz), 5.33-5.31 (t, 1H, J5.5 Hz), 4.38-4.31 (m, 4H), 3.59-3.57 (d, 2H, J 5.5 Hz), 2.20-1.99 (m, 4H), 1.68-1.56 (m, 3H), 1.20 (s, 9H).

Workup

  1. extractionthe resulting mixture extracted with 1 mL EtOAc
  2. extractionThe EtOAc extract
  3. washwas washed with water (2×1 ml)
  4. customthe solvent removed by vacuum centrifugation over 48 h
  5. dissolutionThe resulting solid was dissolved in 450 ml DMF
  6. custompurified by reverse phase preparatory HPLC (Zorbax 2.5×7 cm C8 column, linear gradient 5-100% CH3CH/H2O (0.1% TFA), 15 mL/Min)
  7. customthe solvent removed by vacuum centrifugation
  8. customto give
  9. waitplaced on a speed vacuum overnight for 15 h

Sources & evidence

ORD record
ord-e2879b5deafa4e21ab4c2f9d21f06853
Source dataset
uspto-grants-2003_02
Patent number
US06515023B2

Reaction notes

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