Hydrochloric Acid → HCID 11466777, compound

HRID 1270997Notes

Reaction equation

HRID 1270997 reaction equation
[Cl:1][C:2]1[CH:37]=[CH:36][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([NH:13][CH2:14][C:15]([NH:17][C@@H:18]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)C(NCCN3CCCC3)=O)=[O:16])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.Cl.C1[CH:40]=[CH:41][C:42]2N(O)N=[N:45][C:43]=2C=1.CCN=C=NCCCN(C)C.Cl.ClC1C=CC(OC2C=C[C:70]([NH:73][CH2:74][C:75](O)=O)=[CH:69]C=2)=CC=1.CN1CC[O:84]CC1>C(Cl)Cl.O1CCOCC1.CN(C=O)C.O>[Cl:1][C:2]1[CH:37]=[CH:36][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([NH:13][CH2:14][C:15]([NH:17][C@@H:18]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:69][C:70]([NH:73][CH2:74][CH2:75][N:45]3[CH2:40][CH2:41][CH2:42][CH2:43]3)=[O:84])=[O:16])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11272398HCID 11272398, compoundHCID 18450251HCID 18450251, compound

Product 1

HCID 11466777HCID 11466777, compoundYield 42%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of [(S)-1-benzyl-2-(2-pyrrolidin-1-yl-ethylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester (Example 27, step A, 0.26 g, 2.6 mmol) in CH2Cl2 (5 mL) was added 4 M HCl solution in 1,4-dioxane (2 mL). The mixture was stirred at rt for 4 h, and then the solvent was removed. The residue was redissolved in MeOH (10 mL) and treated with basic resin (Dowex 550A OH anion-exchange resin) for 2 h. The resin was filtered off, and the solvents were removed from the filtrate under reduced pressure. The residue was dissolved in DMF (1 mL) and added to a solution of HOBT (0.095 g, 0.7 mmol), EDCl (0.134 g, 0.7 mmol) and [4-(4-chloro-phenoxy)-phenylamino]-acetic acid (0.13 g, 0.47 mmol) in DMF (5 mL). N-Methyl-morpholine (0.095 g, 0.94 mmol) was then added dropwise. The reaction mixture was stirred at rt overnight, and H2O (10 mL) was then added. The aqueous layer was extracted with EtOAc (3×30 mL). The combined organic layers were washed with 1 N NaOH (2×10 mL) and brine (30 mL), dried (MgSO4), and concentrated. Purification by column chromatography [0–20% (1% NH4OH/MeOH)/CH2Cl2] afforded 0.104 g (42%) of the desired product. MS (electrospray): mass calculated for C30H35ClN4O3, 534.24; m/z found, 535.24 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.63 (d, J=8.6 Hz, 1H), 7.19–7.13 (m, 6H), 7.10–7.08 (m, 2H), 6.80–6.76 (m, 4H), 6.58–6.45 (m, 2H), 6.13 (s, 1H), 4.43–4.40 (m, 1H), 4.18 (s, 1H), 3.72–3.65 (m, 2H), 3.34–3.27 (m, 1H), 3.25–3.16 (m, 1H), 2.92 (dd, J=13.6, 6.5 Hz, 1H), 2.71 (dd, J=13.6, 8.1 Hz, 1H), 2.51 (t, J=6.0 Hz, 2H), 2.44 (s, 4H), 2.33 (dd, J=15.0, 4.87 Hz, 1H), 2.21 (dd, J=15.1, 5.37 Hz, 1H), 1.81 (s, 2H), 1.71 (s, 4H).

Workup

  1. customthe solvent was removed
  2. dissolutionThe residue was redissolved in MeOH (10 mL)
  3. additiontreated with basic resin (Dowex 550A OH anion-exchange resin) for 2 h
  4. filtrationThe resin was filtered off
  5. customthe solvents were removed from the filtrate under reduced pressure
  6. dissolutionThe residue was dissolved in DMF (1 mL)
  7. stirringThe reaction mixture was stirred at rt overnight
  8. extractionThe aqueous layer was extracted with EtOAc (3×30 mL)
  9. washThe combined organic layers were washed with 1 N NaOH (2×10 mL) and brine (30 mL)
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated
  12. customPurification by column chromatography [0–20% (1% NH4OH/MeOH)/CH2Cl2]

Sources & evidence

ORD record
ord-21b3677e8baa4aca852aadf250788d71
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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