Hydrochloric Acid → HCID 24764989, compound

HRID 1806044Notes

Reaction equation

HRID 1806044 reaction equation
[Na+].[Cl:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([O-:9])=O)=[CH:5][C:4]=1[O:12][C:13]1[C:14]([NH:28][C:29]2[S:30][CH:31]=[C:32]([CH3:34])[N:33]=2)=[N:15][CH:16]=[C:17]([S:19][CH:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[CH3:21])[CH:18]=1.C([Cl:40])(=O)OCC.[CH3:41][N:42]([CH3:46])[CH2:43][CH2:44][NH2:45].[OH-].[Na+].[ClH:49]>C(Cl)Cl.CCOCC>[ClH:2].[ClH:40].[ClH:49].[Cl:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:45][CH2:44][CH2:43][N:42]([CH3:46])[CH3:41])=[O:9])=[CH:5][C:4]=1[O:12][C:13]1[C:14]([NH:28][C:29]2[S:30][CH:31]=[C:32]([CH3:34])[N:33]=2)=[N:15][CH:16]=[C:17]([S:19][CH:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[CH3:21])[CH:18]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 66053N,N-DimethylethylenediamineHCID 24764987HCID 24764987, 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-a9ae7ea107db438bb2cd9431d8d11f58
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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