Triethylamine → 4-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzamide hydrochloride

HRID 910996Notes

Reaction equation

HRID 910996 reaction equation
Cl.[Cl:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][C:4]=1[O:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]2[S:21][CH:22]=[C:23]([CH3:25])[N:24]=2)[CH:14]=1.C(N(CC)CC)C.C(Cl)(=O)OCC.[CH3:39][N:40]([CH3:44])[CH2:41][CH2:42][NH2:43].[OH-].[Na+]>CN(C=O)C>[ClH:2].[Cl:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:43][CH2:42][CH2:41][N:40]([CH3:44])[CH3:39])=[O:9])=[CH:5][C:4]=1[O:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]2[S:21][CH:22]=[C:23]([CH3:25])[N:24]=2)[CH:14]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 66053N,N-DimethylethylenediamineHCID 248266634-Chloro-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzoic acid hydrochloride

Product 1

HCID 248266654-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzamide hydrochlorideYield 28.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A 3 dram vial was charged with 4-chloro-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzoic acid hydrochloride (0.100 g, 0.2511 mmol), triethylamine (0.1016 g, 1.004 mmol) and DMF (3 mL). The reaction mixture was cooled to 0° C. and ethyl carbonochloridate (0.02641 mL, 0.2762 mmol) was added. The reaction mixture was at 0° C. for 3 hours. N,N-dimethylethylenediamine (0.04427 g, 0.5022 mmol) was added and the reaction mixture was stirred at room temperature overnight, and then 2N NaOH was added. The reaction mixture was extracted with ethyl acetate, dried over magnesium sulfate, filtered and concentrated. The residue was purified using prepacked silica gel column with 50% ethyl acetate in hexanes followed by 15% (ammoniated) methanol in ethyl acetate. 2M HCl in ether was added and the resulting solids were dried over high vacuum to afford 4-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzamide hydrochloride (0.017 g, 13.01% yield) as an off white solid. 1H NMR (DMSO) δ 11.21 (bs, 1H), 9.82 (bs, 1H), 8.95 (t, 1H), 8.24 (d, 1H), 7.90 (dd, 1H), 7.86 (d, 1H), 7.84 (d, 1H), 6.57 (m, 3H), 3.61 (q, 2H), 3.24 (q, 2H), 2.82 (s, 3H), 2.81 (s, 3H), 2.21 (d, 3H); Mass spectrum (esi) m/z=432 (100) (M+H—HCl).

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified
  6. addition2M HCl in ether was added
  7. customthe resulting solids were dried over high vacuum

Sources & evidence

ORD record
ord-92185b409cb7434b81442e40143714b3
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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