HCID 76577160, compound → HCID 57828218, compound

HRID 1644238Notes

Reaction equation

HRID 1644238 reaction equation
[C:1]([O:5][C:6](=[O:29])[NH:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH:22]=[CH:23][CH2:24][CH2:25][N:26]=[N+]=[N-])=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2]>C(O)C.[Pd]>[C:1]([O:5][C:6](=[O:29])[NH:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH2:22][CH2:23][CH2:24][CH2:25][NH2:26])=[CH:14][CH:13]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

4

Reactant 1

HCID 76577160HCID 76577160, compound

Product 1

HCID 57828218HCID 57828218, compoundYield 89.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

{3-[4-(4-Azido-but-1-enyl)-naphthalen-1-yloxy]-propyl}-carbamic acid tert-butyl ester 3.5 g was hydrogenated in ethanol with 5% Pd/C (50% wet) for 2 h. Catalyst was removed, and the filtrate was concentrated to give 2.94 g of {3-[4-(4-Amino-butyl)-naphthalen-1-yloxy]-propyl}-carbamic acid tert-butyl ester. One gram (2.66 mmol) of free amine was stirred with 1-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-2-methyl-isothiourea (1.55 g, 3.99 mmol) in dry ethanol (25 mL). Diisopropyl-ethylamine (1.39 mL, 7.98 mmol) of was added and the reaction mixture was warmed to 45° C. overnight. Ethanol was added and the reaction filtered. After concentration of the filtrate, the residue was purified by flash chromatography (0-10% MeOH/CH2Cl2) to give 0.92 g of [3-(4-{4-[N′-(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-guanidino]-butyl}-naphthalen-1-yloxy)-propyl]-carbamic acid tert-butyl ester. [3-(4-{4-[N′-(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-guanidino]-butyl}1-naphthalen-1-yloxy)-propyl]-carbamic acid tert-butyl ester (2.7 g was stirred with 4M HCl in p-dioxane for 1 hour at room temperature. Solvents were removed in vacuo. A small amount of the product was purified by flash chromatography to give 7 GS-426675 N-{4-[4-(3-Amino-propoxy)-naphthalen-1-yl]-butyl}-N′-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-guanidine as an HCl salt.

Workup

  1. customCatalyst was removed
  2. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-9e8902e46fca4f7eab095db745460fa4
Source dataset
uspto-grants-2012_02
Patent number
US08124607B2

Reaction notes

Loading…