Hydrochloric Acid → HCID 11751765, compound

HRID 1270987Notes

Reaction equation

HRID 1270987 reaction equation
[C:1]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:6]=[CH:5][C:4]([N:7]=[C:8](NC#N)[NH:9][C@@H:10]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:11]([NH:13][CH2:14][CH2:15][CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:12])=[CH:3][CH:2]=1.Cl.[O:39]1CCOCC1.N(C1C=CC(C2C=CC=CC=2)=CC=1)=C=O>C(Cl)Cl.CCOC(C)=O>[C:1]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:6]=[CH:5][C:4]([NH:7][C:8](=[O:39])[NH:9][C@@H:10]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:11]([NH:13][CH2:14][CH2:15][CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:12])=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 36123194-Biphenylyl isocyanateHCID 178512239HCID 178512239, compound

Product 1

HCID 11751765HCID 11751765, compoundYield 77.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [(S)-2-phenyl-1-(3-pyrrolidin-1-yl-propylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester (Example 1, step A) (0.083 g, 0.22 mmol) in CH2Cl2 (3 mL), a 4 M solution of HCl in dioxane (0.55 mL, 2.2 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 under reduced pressure. The residue was dissolved in CH2Cl2 (3 mL), and at 0° C., TEA (0.56 g, 0.55 mmol) was added followed by 4-isocyanato-biphenyl (0.052 g, 0.264 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 was dried (Na2SO4). The solvent was removed, and the residue was purified by flash column chromatography using 0–20% MeOH (1% NH4OH)/CH2Cl2 to afford 0.08 g (77%) of the desired product. MS (electrospray): mass calculated for C29H34N4O2, 470.27; m/z found, 471.3 [M+H]+. 1H NMR (400 MHz, CD3OD): 7.56–7.48 (m, 4H), 7.42–7.36 (m, 4H), 7.33–7.22 (m, 6H), 4.47 (t, J=7.1 Hz, 1H), 3.20–3.16 (m, 2H), 3.07 (dd, J=13.6, 7.1 Hz, 1H), 2.99 (dd, J=13.6, 7.1 Hz 1H), 2.51 (br m, 4H), 2.42 (m, 2H), 1.77 (br m, 4H), 1.65 (m, 2H).

Workup

  1. customThe solvents were removed
  2. additionThe residue was treated with CH2Cl2
  3. customthe solvent was removed again under reduced pressure
  4. dissolutionThe residue 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 materialwas dried (Na2SO4)
  8. customThe solvent was removed
  9. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-b8a63aa32b2d4ccd85717c4cbf9d194b
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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