Ammonium Chloride → HCID 89544903, compound

HRID 2283397Notes

Reaction equation

HRID 2283397 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:12]1[C:13]([F:30])=[C:14]([C:26]([Cl:29])=[CH:27][CH:28]=1)[C:15]([C:17]1[CH:18]=[CH:19][C:20]([C:23](O)=[O:24])=[N:21][CH:22]=1)=[O:16])[CH2:10][CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-].[NH4+].CC[N:35](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([C:12]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:14]([C:15]([C:17]2[CH:22]=[N:21][C:20]([C:23](=[O:24])[NH2:35])=[CH:19][CH:18]=2)=[O:16])[C:13]=1[F:30])[CH2:10][CH3:11])([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 89544599HCID 89544599, compound

Product 1

HCID 89544903HCID 89544903, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

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. washwashed with water
  2. extractionThe organic extract
  3. dry with materialwas dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurified by Prep HPLC

Sources & evidence

ORD record
ord-b3dc6ecbfae04e83bc484029d5e0d709
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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