Hydrochloric Acid → HCID 24764989, compound

HRID 335112Notes

Reaction equation

HRID 335112 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[O:11][C:12]1[C:13]([NH:27][C:28]2[S:29][CH:30]=[C:31]([CH3:33])[N:32]=2)=[N:14][CH:15]=[C:16]([S:18][CH:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[CH3:20])[CH:17]=1.C(OC([Cl:39])=O)C.[CH3:40][N:41]([CH3:45])[CH2:42][CH2:43][NH2:44].[OH-].[Na+].[ClH:48]>C(Cl)Cl.CCOCC>[ClH:1].[ClH:39].[ClH:48].[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:44][CH2:43][CH2:42][N:41]([CH3:45])[CH3:40])=[O:8])=[CH:4][C:3]=1[O:11][C:12]1[C:13]([NH:27][C:28]2[S:29][CH:30]=[C:31]([CH3:33])[N:32]=2)=[N:14][CH:15]=[C:16]([S:18][CH:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[CH3:20])[CH:17]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 66053N,N-DimethylethylenediamineHCID 24764988HCID 24764988, compound

Product 1

HCID 24764989HCID 24764989, compoundYield 14.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

4-chloro-3-(2-(4-methylthiazol-2-ylamino)-5-(1-(pyridin-2-yl)ethylthio)pyridin-3-yloxy)benzoic acid (prepared according to Example 73; 0.131 g, 0.263 mmol), TEA (d. 0.726) (0.0732 mL, 0.525 mmol), ethyl-carbonochloridate (0.057 g, 0.525 mmol), and N1,N1-dimethylethane-1,2-diamine (0.0231 g, 0.263 mmol) were reacted according the method of Example 72. 1N NaOH was added and the reaction mixture was stirred for 3 hours. The reaction mixture was extracted with CH2Cl2. The combined extracts were concentrated and purified by silica gel chromatography (4% MeOH in CH2Cl2, using 2% 7N ammonia in MeOH) and then purified by reverse phase chromatography to give the compound as the free base. The free base was dissolved in CH2Cl2 and HCl in ether was added. The mixture was concentrated to give 4-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazol-2-ylamino)-5-(1-(pyridin-2-yl)ethylthio)pyridin-3-yloxy)benzamide trihydrochloride (0.025 g, 14.8% yield). 1H NMR (d6-DMSO) δ 9.73 (s, 1H), 8.91 (m, 1H), 8.42 (m, 1H), 8.01 (d, 1H), 7.78 (m, 3H), 7.51 (s, 1H), 7.29 (m, 2H), 6.83 (s, 1H), 6.66 (m, 1H), 4.48 (q, 1H), 3.60 (m, 2H), 3.24 (m, 2H), 2.81 (d, 6H), 2.24 (s, 3H), 1.54 (d, 3H); Mass spectrum (esi) m/z=569.2 (100) (M+H-3HCl).

Workup

  1. extractionThe reaction mixture was extracted with CH2Cl2
  2. concentrationThe combined extracts were concentrated
  3. custompurified by silica gel chromatography (4% MeOH in CH2Cl2, using 2% 7N ammonia in MeOH)
  4. custompurified by reverse phase chromatography
  5. customto give the compound as the free base
  6. concentrationThe mixture was concentrated

Sources & evidence

ORD record
ord-887a95df0756402e8528e7b854a6c7af
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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