Hydrogen chloride-ethyl acetate → HCID 89544793, compound

HRID 2283398Notes

Reaction equation

HRID 2283398 reaction equation
C(OC(=O)[NH:7][C@@H:8]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([C:18]([C:20]2[CH:21]=[N:22][C:23]([C:26](=[O:28])[NH2:27])=[CH:24][CH:25]=2)=[O:19])[C:12]=1[F:29])[CH2:9][CH3:10])(C)(C)C.Cl.CCOC(C)=O>>[NH2:7][C@@H:8]([C:11]1[C:12]([F:29])=[C:13]([C:14]([Cl:17])=[CH:15][CH:16]=1)[C:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]([NH2:27])=[O:28])=[N:22][CH:21]=1)=[O:19])[CH2:9][CH3:10]

Participants

3

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 89544903HCID 89544903, compound

Product 1

HCID 89544793HCID 89544793, compoundYield 54.3%

Procedure

To a solution of 5-[3-((R)-1-tert-Butoxycarbonylamino-propyl)-6-chloro-2-fluoro-benzoyl]-pyridine-2-carboxylic acid (Example 19)) in dichloromethane (8 ml) was added ammonium chloride (0.057 g, 0.65 mmol), DIPEA (0.137 mL, 0.78 mmol) and then HATU (0.06 g, 0.156 mmol) and the reaction stirred for 1 h. Further HATU totalling (0.12 g, 0.312 mmol) added. The reaction performed on a further (57 mg), both reactions combined and diluted with dichloromethane washed with water. The organic extract was dried (Na2SO4), filtered and concentrated. Purified by Prep HPLC to give {(R)-1-[3-(6-Carbamoyl-pyridine-3-carbonyl)-4-chloro-2-fluoro-phenyl]-propyl}-carbamic acid tert-butyl ester (0.042 g) MS: [M+H] 436 {(R)-1-[3-(6-Carbamoyl-pyridine-3-carbonyl)-4-chloro-2-fluoro-phenyl]-propyl}-carbamic acid tert-butyl ester (0.042 g, 0.137 mmol) treated with saturated HCl/EtOAc stirred at ambient for 1 hour, precipitate filtered and washed with ether to give 5-[3-((R)-1-amino-propyl)-6-chloro-2-fluoro-benzoyl]-pyridine-2-carboxylic acid amide (0.025 g).

Workup

  1. filtrationprecipitate filtered
  2. washwashed with ether

Sources & evidence

ORD record
ord-04a77f89b4564ea98f3ad0470fa0f4b9
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

Loading…