Triethylamine → HCID 69951628, compound

HRID 1532364Notes

Reaction equation

HRID 1532364 reaction equation
[CH2:1]([O:8][C:9]([N:11]([CH2:37][CH2:38][CH2:39][CH2:40][C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1)[CH2:12][CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:23]([CH3:28])([CH3:27])[C:24]([OH:26])=O)[CH:21]=2)[NH:16][C:15]=1[C:29]1[CH:34]=[C:33]([CH3:35])[CH:32]=[C:31]([CH3:36])[CH:30]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH:48]12[NH:54][CH:51]([CH2:52][CH2:53]1)[CH2:50][CH2:49]2.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl.CO.C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:10])[N:11]([CH2:12][CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:23]([CH3:28])([CH3:27])[C:24]([N:54]3[CH:48]4[CH2:53][CH2:52][CH:51]3[CH2:50][CH2:49]4)=[O:26])[CH:21]=2)[NH:16][C:15]=1[C:29]1[CH:34]=[C:33]([CH3:35])[CH:32]=[C:31]([CH3:36])[CH:30]=1)[CH2:37][CH2:38][CH2:39][CH2:40][C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 162795037-Azabicyclo[2.2.1]heptane hydrochlorideHCID 21249907HCID 21249907, compound

Product 1

HCID 69951628HCID 69951628, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of of 92.7 mg (0.15 mmol) of 2-[3-[2-[benzyloxycarbonyl-[4-(pyridin-3-yl)butyl]amino]ethyl]-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropionic acid, 80.2 mg (0.6 mmol) of 7-azabicyclo[2.2.1]heptane hydrochloride, 83.2 mg (0.16 mmol) of PyBOP reagent, 0.107 mL (77.8 mg; 0.77 mmol) of triethylamine, and 0.75 mL of dry methylene chloride was stirred at room temperature in a stoppered flask for 48 hours. The solution was then partitioned between 10 mL of ethyl acetate and 10 mL of 0.5 N hydrochloric acid. The organic phase was washed with 10 mL of saturated aqueous sodium bicarbonate solution and then with 5 mL of saturated aqueous sodium chloride solution. The ethyl acetate phase was then dried (magnesium sulfate), filtered, and concentrated in vacuo at room temperature. The residue was purified by preparative TLC on 6 Analtech tapered silica gel plates (20×20 cm), which were developed in 95:5 CH2Cl2-MeOH. The product band from each plate was isolated, combined, and extracted with 95:5 CH2Cl2-MeOH. Concentration of the extracts in vacuo yielded 85.9 mg (82%) of a very pale yellow glass; virtually homogeneous by TLC in 95:5 CH2Cl2-MeOH. 506 MHz 1H NMR (CDCl3) was complex, owing to rotamers, but was consistent with the assigned structure. Mass spectrum (ESI): m/e=697.6 (M+H).

Workup

  1. customThe solution was then partitioned between 10 mL of ethyl acetate and 10 mL of 0.5 N hydrochloric acid
  2. washThe organic phase was washed with 10 mL of saturated aqueous sodium bicarbonate solution
  3. dry with materialThe ethyl acetate phase was then dried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo at room temperature
  6. customThe residue was purified by preparative TLC on 6 Analtech
  7. customThe product band from each plate was isolated
  8. extractionextracted with 95:5 CH2Cl2-MeOH
  9. customConcentration of the extracts in vacuo yielded 85.9 mg (82%) of a very pale yellow glass

Sources & evidence

ORD record
ord-c8d702177a834ee3847a3186613e0192
Source dataset
uspto-grants-2001_03
Patent number
US06200957B1

Reaction notes

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