Hydrochloric Acid → HCID 11752425, compound

HRID 1270985Notes

Reaction equation

HRID 1270985 reaction equation
Cl[C:2]1[CH:38]=[CH:37][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:36])[NH:15][C@@H:16]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:17]([NH:19][CH2:20][CH2:21][N:22]([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])=[O:18])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.Cl.O1CCOCC1.C(N(CC)CC)C.O(C1C=CC(N=C=O)=CC=1)C1C=CC=CC=1>C(Cl)Cl.CCOC(C)=O>[CH:26]([N:22]([CH:23]([CH3:25])[CH3:24])[CH2:21][CH2:20][NH:19][C:17](=[O:18])[C@@H:16]([NH:15][C:14]([NH:13][C:10]1[CH:11]=[CH:12][C:7]([O:6][C:5]2[CH:37]=[CH:38][CH:2]=[CH:3][CH:4]=2)=[CH:8][CH:9]=1)=[O:36])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([CH3:27])[CH3:28]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 27348964-Phenoxyphenyl isocyanateHCID 10459847HCID 10459847, compound

Product 1

HCID 11752425HCID 11752425, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [(S)-1-(2-diisopropylamino-ethylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester (Example 3, step B) (0.1 g, 0.258 mmol) in CH2Cl2 (3 mL), a 4 M solution of HCl in dioxane (0.64 mL, 2.56 mmol) was added, and the mixture was stirred for 3 h at rt. The solvents were removed, the residue was treated with CH2Cl2, and the solvent was removed again. The crude product was dissolved in CH2Cl2 (3 mL), and triethylamine (0.037 g, 0.365 mmol) was added at 0° C. followed by 4-phenoxyphenylisocyanate (0.059 g, 0.28 mmol). The mixture was warmed to rt over a period of 2 h and was then diluted with EtOAc (100 mL). The organic layer was washed with saturated NaHCO3 (25 mL) and brine (25 mL), and dried (Na2SO4). The solvent was removed, and the residue was purified by flash column chromatography using 0–20% MeOH (1% NH4OH)/CH2Cl2 to afford 0.07 g (55%) of the desired product. MS (electrospray): mass calculated for C30H38N4O3, 502.29; m/z found, 503.3 [M+H]+. 1H NMR (400 MHz, CD3OD): 7.3–7.19 (m, 9H), 7.04 (m, 1H), 6.91–6.85 (m, 4H), 4.47 (t, J=7.4 Hz, 1H), 3.19–2.95 (m, 6H), 2.42 (br s, 2H), 1.02 (d, J=6.4 Hz, 12H).

Workup

  1. customThe solvents were removed
  2. additionthe residue was treated with CH2Cl2
  3. customthe solvent was removed again
  4. dissolutionThe crude product was dissolved in CH2Cl2 (3 mL)
  5. temperatureThe mixture was warmed to rt over a period of 2 h
  6. washThe organic layer was washed with saturated NaHCO3 (25 mL) and brine (25 mL)
  7. dry with materialdried (Na2SO4)
  8. customThe solvent was removed
  9. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-6e2c129c356f447aa34812ee9957e1fa
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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