Hydrochloric Acid → N-[3-Carbamoyl-4-[1-(4,5-dihydro-3H-pyrrol-2-yl)piperidin-4-yloxy]phenyl]-N-[3-[3-(ethoxycarbonylamino)(imino)methylphenyl]-2-(E)-propeny]methanesulfonamide Dihydrochloride

HRID 1796192Notes

Reaction equation

HRID 1796192 reaction equation
[ClH:1].Cl.C([C:6]1[CH:7]=[C:8](/[CH:12]=[CH:13]/[CH2:14][N:15]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH:27]3[CH2:32][CH2:31][N:30]([C:33]4[CH2:37][CH2:36][CH2:35][N:34]=4)[CH2:29][CH2:28]3)=[C:22]([C:38](=[O:40])[NH2:39])[CH:21]=2)[S:16]([CH3:19])(=[O:18])=[O:17])[CH:9]=[CH:10][CH:11]=1)(=N)N.[C:41](=[O:55])([O:45][C:46]1[CH:51]=CC([N+]([O-])=O)=CC=1)OCC.C([N:58]([CH2:61]C)CC)C.Cl.C[N:65](C)C=O>ClCCl.O1CCOCC1.O>[ClH:1].[ClH:1].[C:38]([C:22]1[CH:21]=[C:20]([N:15]([CH2:14]/[CH:13]=[CH:12]/[C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([NH:65][C:41]([O:45][CH2:46][CH3:51])=[O:55])[C:7]=2[CH:61]=[NH:58])[S:16]([CH3:19])(=[O:18])=[O:17])[CH:25]=[CH:24][C:23]=1[O:26][CH:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH2:37][CH2:36][CH2:35][N:34]=2)[CH2:29][CH2:28]1)(=[O:40])[NH2:39]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8471TriethylamineHCID 586863Ethyl 4-nitrophenyl carbonateHCID 22180975N-[3-(3-amidinophenyl)-2-(E)-propenyl]-N-[3-carbamoyl-4-[1-(4,5-dihydro-3H-pyrrol-2-yl)piperidin-4-yloxy]phenyl]methanesulfonamide dihydrochloride

Product 1

HCID 86593745N-[3-Carbamoyl-4-[1-(4,5-dihydro-3H-pyrrol-2-yl)piperidin-4-yloxy]phenyl]-N-[3-[3-(ethoxycarbonylamino)(imino)methylphenyl]-2-(E)-propeny]methanesulfonamide DihydrochlorideYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of N-[3-(3-amidinophenyl)-2-(E)-propenyl]-N-[3-carbamoyl-4-[1-(4,5-dihydro-3H-pyrrol-2-yl)piperidin-4-yloxy]phenyl]methanesulfonamide dihydrochloride (0.23 g) obtained in example 99(b) in a mixture of dichloromethane (4.5 ml) and N,N-dimethylformamide (1.5 ml) were added successively ethyl 4-nitrophenyl carbonate (0.10 g) obtained in example 103 and triethylamine (0.16 ml) at room temperature, and the resulting mixture was stirred at room temperature overnight and then evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (50:0˜47:3). Subsequently, to a solution of the oily product obtained in ethanol (2 ml) was added a 4N solution of hydrogen chloride in dioxane (0.5 ml), and the resulting mixture was evaporated to dryness in vacuo. The amorphous solid obtained was dissolved in dichloromethane, and the resulting mixture was extracted with 1N hydrochloric acid, and the aqueous layer collected was evaporated in vacuo. The residue obtained was dissolved in water and then lyophilized to afford the title compound (0.20 g, yield: 84%) as a colorless amorphous solid.

Workup

  1. customevaporated in vacuo
  2. customThe residue obtained
  3. customwas purified by chromatography on a silica gel column
  4. customSubsequently, to a solution of the oily product obtained in ethanol (2 ml)
  5. customthe resulting mixture was evaporated to dryness in vacuo
  6. customThe amorphous solid obtained
  7. extractionthe resulting mixture was extracted with 1N hydrochloric acid
  8. customthe aqueous layer collected
  9. customwas evaporated in vacuo
  10. customThe residue obtained

Sources & evidence

ORD record
ord-de93b66ab61d41a6949b572767a08711
Source dataset
uspto-grants-2006_04
Patent number
US07030138B2

Reaction notes

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