Ethyl chloroformate → HCID 24764898, compound

HRID 335111Notes

Reaction equation

HRID 335111 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[O:11][C:12]1[C:13]([NH:25][C:26]2[S:27][CH:28]=[C:29]([CH3:31])[N:30]=2)=[N:14][CH:15]=[C:16]([S:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:17]=1.C([Cl:37])(=O)OCC.[CH3:38][N:39]([CH3:43])[CH2:40][CH2:41][NH2:42]>O>[ClH:1].[ClH:37].[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:42][CH2:41][CH2:40][N:39]([CH3:43])[CH3:38])=[O:7])=[CH:4][C:3]=1[O:11][C:12]1[C:13]([NH:25][C:26]2[S:27][CH:28]=[C:29]([CH3:31])[N:30]=2)=[N:14][CH:15]=[C:16]([S:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:17]=1

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 66053N,N-DimethylethylenediamineHCID 24764897HCID 24764897, compound

Product 1

HCID 24764898HCID 24764898, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

4-Chloro-3-(2-(4-methylthiazol-2-ylamino)-5-(phenylthio)pyridin-3-yloxy)benzoic acid (prepared according to Example 71; 0.131 g, 0.279 mmol) and TEA (0.117 mL, 0.836 mmol) were placed in a flask and cooled to 0° C. Ethyl carbonochloridate (0.0303 g, 0.279 mmol) was added, and the reaction mixture was stirred at 0° C. for 30 minutes. N1,N1-dimethylethane-1,2-diamine (0.0306 mL, 0.279 mmol) was added, and the reaction mixture was stirred at room temperature for 1 hour. Water was added and the reaction mixture was extracted with CH2Cl2. The organic layer was concentrated and the residue was purified first by silica gel chromatography and then by reverse phase chromatography to provide the desired product as the free base. The free base was dissolved in CH2Cl2 and HCl in ether was added to give 4-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazol-2-ylamino)-5-(phenylthio)pyridin-3-yloxy)benzamide dihydrochloride (0.069 g, 40.4% yield). 1H NMR (d6-DMSO) δ 9.83 (bs, 1H), 8.90 (m, 1H), 8.24 (m, 1H), 7.75 (m, 2H), 7.58 (s, 1H), 7.30 (m, 2H), 7.19 (m, 4H), 6.67 (s, 1H), 3.59 (m, 2H), 3.23 (m, 2H), 2.80 (d, 6H), 2.25 (s, 3H); Mass spectrum (esi) m/z=540.1 (100) (M+H-2HCl).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 1 hour
  2. extractionthe reaction mixture was extracted with CH2Cl2
  3. concentrationThe organic layer was concentrated
  4. customthe residue was purified first by silica gel chromatography

Sources & evidence

ORD record
ord-3cb9d22f961141ce9870060be3ee9de4
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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