Triethylamine → 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

HRID 1796188Notes

Reaction equation

HRID 1796188 reaction equation
[ClH:1].Cl.[C:3]([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][NH:30][CH2:29][CH2:28]3)=[C:22]([C:33](=[O:35])[NH2:34])[CH:21]=2)[S:16]([CH3:19])(=[O:18])=[O:17])[CH:9]=[CH:10][CH:11]=1)(=[NH:5])[NH2:4].CO[C:38]1[CH2:39][CH2:40][CH2:41][N:42]=1.N1CCCC1=O.C(N(CC)CC)C>C(O)C.Cl.O>[ClH:1].[ClH:1].[C:3]([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:38]4[CH2:39][CH2:40][CH2:41][N:42]=4)[CH2:29][CH2:28]3)=[C:22]([C:33](=[O:35])[NH2:34])[CH:21]=2)[S:16]([CH3:19])(=[O:18])=[O:17])[CH:9]=[CH:10][CH:11]=1)(=[NH:4])[NH2:5]

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 120252-PyrrolidoneHCID 3534432-Methoxy-1-Pyrroline2×HCID 22180971N-[3-(3-amidinophenyl)-2-(E)-propenyl]-N-[3-carbamoyl-4-(piperidin-4-yloxy)phenyl]methanesulfonamide dihydrochloride

Product 1

HCID 22180975N-[3-(3-amidinophenyl)-2-(E)-propenyl]-N-[3-carbamoyl-4-[1-(4,5-dihydro-3H-pyrrol-2-yl)piperidin-4-yloxy]phenyl]methanesulfonamide dihydrochlorideYield 125.6%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

To a solution of N-[3-(3-amidinophenyl)-2-(E)-propenyl]-N-[3-carbamoyl-4-(piperidin-4-yloxy)phenyl]methanesulfonamide dihydrochloride (0.95 g) obtained in example 99(a) in ethanol (15 ml) were added successively 5-methoxy-3,4-dihydro-2H-pyrrole (0.52 g), which was prepared from 2-pyrrolidinone according to the method described in Org. Prep. Proced. Int., 24, 147 (1992), and triethylamine (1.20 ml) at room temperature, and the resulting mixture was allowed to stand at room temperature overnight, and at the end of this time, 5-methoxy-3,4-dihydro-2H-pyrrole (0.17 g) and triethylamine (0.24 ml) were furthermore added successively, and the resulting mixture was stirred at room temperature for 6 hours and then evaporated in vacuo. Subsequently, to the residue obtained were added successively ethanol (10 ml) and a 4N solution of hydrogen chloride in dioxane (4 ml), and the resulting mixture was evaporated in vacuo. The residue obtained was purified by preparative HPLC (YMC-Pack ODS-A; YMC, eluent: 10% acetonitrile/water). The amorphous solid obtained was dissolved in 1N hydrochloric acid (5 ml), and the resulting mixture was evaporated to dryness in vacuo. The, residue obtained was dissolved in water and then lyophilized to afford the title compound (0.67 g, yield: 63%) as a colorless amorphous solid.

Workup

  1. customat room temperature
  2. customevaporated in vacuo
  3. customSubsequently, to the residue obtained
  4. customa 4N solution of hydrogen chloride in dioxane (4 ml), and the resulting mixture was evaporated in vacuo
  5. customThe residue obtained
  6. customwas purified by preparative HPLC (YMC-Pack ODS-A; YMC, eluent: 10% acetonitrile/water)
  7. customThe amorphous solid obtained
  8. customthe resulting mixture was evaporated to dryness in vacuo
  9. customThe, residue obtained

Sources & evidence

ORD record
ord-d34bbe5e77034ef1912311d745822263
Source dataset
uspto-grants-2006_04
Patent number
US07030138B2

Reaction notes

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