Hydrochloric Acid → HCID 58843178, compound

HRID 1271004Notes

Reaction equation

HRID 1271004 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:35])[NH:16][C@@H:17]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:18]([NH:20][CH2:21][CH2:22][N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1C=CC(OC2C=CC(NC(=S)N[C@@H](CC3C=CC=CC=3)C(NCCN3CCCC3)=O)=CC=2)=CC=1.Cl.O1CCOCC1.O(C1C=CC(N=C=O)=CC=1)C1C=CC=CC=1>C(Cl)Cl.CCOC(C)=O>[CH2:28]([C@H:17]([NH:16][C:15]([NH:14][C:11]1[CH:10]=[CH:9][C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:13][CH:12]=1)=[O:35])[CH2:18][NH:20][CH2:21][CH2:22][N:23]1[CH2:24][CH2:25][CH2:26][CH2:27]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 27348964-Phenoxyphenyl isocyanateHCID 58843147(S)-2-{3-[4-(4-Chloro-phenoxy)-phenyl]-thioureido}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamideHCID 69432798(S)-2-[3-(4-Phenoxy-phenyl)-ureido]-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide

Product 1

HCID 58843178HCID 58843178, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-[3-(4-Phenoxy-phenyl)-ureido]-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide. To a solution of [(S)-2-phenyl-1-(2-pyrrolidin-1-yl-ethylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester (Example 9, step A) (0.1 g, 0.28 mmol) in CH2Cl2 (3 mL), a 4 M solution of HCl in dioxane (2.5 mL, 10 mmol) was added, and the mixture was stirred for 4 h at rt. The solvents were removed, and the residue was treated with CH2Cl2. The solvents were removed again under reduced pressure. The residue was dissolved in CH2Cl2 (3 mL), and TEA (0.07 g, 0.69 mmol) was added at 0° C. followed by 4-phenoxyphenylisocyanate (0.07 g, 0.33 mmol). The mixture was warmed to rt over a period of 4 h and then diluted with EtOAc (75 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 0.03 g (25%) of the desired product. MS (electrospray): mass calculated for C28H32N4O3, 472.25; m/z found, 473.2 [M+H]+, 495.2 [M+Na]+. 1H NMR (400 MHz, DMSO-d6): 8.68 (s, 1H), 8.04 (t, J=5.5 Hz, 1H), 7.36–6.89 (m, 14H), 6.30 (d, J=8.3 Hz, 1H), 4.46 (m, 1H), 3.15 (m, 2H), 2.96 (dd, J=13.6, 5.6 Hz, 1H), 2.82 (dd, J=13.6, 7.7 Hz, 1H), 2.42–2.37 (m, 6H), 1.67–1.63 (m, 4H).

Workup

  1. customThe solvents were removed
  2. additionthe residue was treated with CH2Cl2
  3. customThe solvents were 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 4 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-46551ea091544219ae0fba89e4cf81c3
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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