4,6-Dichloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidine → 5-Isopropyl-pyridine-2-sulfonic acid 6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl-amide

HRID 356655

Reaction equation

HRID 356655 reaction equation
Cl[C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH3:16])=[C:6]([Cl:17])[N:5]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:3]=1.[K+].[CH:25]([C:28]1[CH:29]=[CH:30][C:31]([S:34]([NH-:37])(=[O:36])=[O:35])=[N:32][CH:33]=1)([CH3:27])[CH3:26]>CS(C)=O>[Cl:17][C:6]1[N:5]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:3]=[C:2]([NH:37][S:34]([C:31]2[CH:30]=[CH:29][C:28]([CH:25]([CH3:27])[CH3:26])=[CH:33][N:32]=2)(=[O:36])=[O:35])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH3:16]

Participants

4

Reactant 2

HCID 219795314,6-Dichloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidineHCID 1317209445-Isopropyl pyridine-2-sulfonamide potassium salt

Product 1

HCID 227294065-Isopropyl-pyridine-2-sulfonic acid 6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl-amideYield 96.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 1.18 g of 4,6-dichloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidine and 2.12 g (8.88 mmol) of 5-isopropyl-pyridine-2-sulphonamide potassium salt in 25 ml of dry DMSO was heated to 80° C. for 3 hours until the dichloride had disappeared completely. The DMSO was removed in a high vacuum, the residue was taken up with 60 ml of water and the aqueous solution was washed three times with diethyl ether. The solution was then acidified to pH 3.5 with 1N HCl and the product was extracted three times with ethyl acetate. The organic phases were washed twice with water and finally once with saturated sodium chloride solution, combined, dried with sodium sulphate and evaporated. The crystalline residue was digested twice with absolute diethyl ether in order to completely remove a trace of 5-isopropyl-pyridine-2-sulphonamide. The crystals remaining behind were filtered off and dried. There were obtained 1.66 g (96%) of 5-isopropyl-pyridine-2-sulphonic acid 6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-ylamide as white crystals of m.p. 168°-176° C., MS: (M-H)- =518.3.

Workup

  1. customThe DMSO was removed in a high vacuum
  2. washthe aqueous solution was washed three times with diethyl ether
  3. extractionthe product was extracted three times with ethyl acetate
  4. washThe organic phases were washed twice with water and finally once with saturated sodium chloride solution
  5. dry with materialdried with sodium sulphate
  6. customevaporated
  7. customto completely remove a trace of 5-isopropyl-pyridine-2-sulphonamide
  8. filtrationThe crystals remaining behind were filtered off
  9. customdried

Sources & evidence

ORD record
ord-587d000b43c7457b8e3652f38cd3d8fa
Source dataset
uspto-grants-1998_11
Patent number
US05837708

Linked notes

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