Ether hydrochloride → N*2*-(1,1-dioxo-hexahydro-1 lambda*6*-thiopyran-4-yl)-5-(2-isopropyl-4,5-dimethoxy-phenoxy)-pyrimidine-2,4-diamine HCl salt

HRID 81755Notes

Reaction equation

HRID 81755 reaction equation
[CH:1]([C:4]1[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[CH:21][C:5]=1[O:6][C:7]1[C:8]([NH2:20])=[N:9][C:10]([NH:13][CH:14]2[CH2:19][CH2:18]S[CH2:16][CH2:15]2)=[N:11][CH:12]=1)([CH3:3])[CH3:2].O[O:30][S:31]([O-:33])=O.[K+].[ClH:35].CCOCC>CO.O>[ClH:35].[O:30]=[S:31]1(=[O:33])[CH2:18][CH2:19][CH:14]([NH:13][C:10]2[N:9]=[C:8]([NH2:20])[C:7]([O:6][C:5]3[CH:21]=[C:22]([O:27][CH3:28])[C:23]([O:25][CH3:26])=[CH:24][C:4]=3[CH:1]([CH3:3])[CH3:2])=[CH:12][N:11]=2)[CH2:15][CH2:16]1

Participants

6

Reactant 3

HCID 10953452Ether hydrochlorideHCID 23707502Potassium hydroxy sulfiteHCID 67333774HCID 67333774, compound

Product 1

HCID 86762022N*2*-(1,1-dioxo-hexahydro-1 lambda*6*-thiopyran-4-yl)-5-(2-isopropyl-4,5-dimethoxy-phenoxy)-pyrimidine-2,4-diamine HCl salt

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

To a mixture of 5-(2-isopropyl-4,5-dimethoxy-phenoxy)-N*2*-(tetrahydro-thiopyran-4-yl)-pyrimidine-2,4-diamine (0.19 g, 0.46 mmol) in 25 mL of methanol and 25 mL of water was added the OXONE (1.73 g, 1.4 mmol). This mixture was stirred at room temperature overnight. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc (3×50 mL). The organic solution was washed with Brine, dried over MgSO4. The solution was filtered and concentrated. The residue was purified on one preparative TLC plate (20×40 cm) eluting with EtOAc. Product recovered was stirred with 1.5 eq of 1M HCl/ether to afford 25 mg of N*2*-(1,1-dioxo-hexahydro-1lambda*6*-thiopyran-4-yl)-5-(2-isopropyl-4,5-dimethoxy-phenoxy)-pyrimidine-2,4-diamine HCl salt): MS (M+H); 441: MP; 255.1-257.8° C.

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. washThe organic solution was washed with Brine
  3. dry with materialdried over MgSO4
  4. filtrationThe solution was filtered
  5. concentrationconcentrated
  6. customThe residue was purified on one preparative TLC plate (20×40 cm)
  7. washeluting with EtOAc
  8. customProduct recovered

Sources & evidence

ORD record
ord-3d564fbc25a94ed5b02b4d8d73f5e7a7
Source dataset
uspto-grants-2014_09
Patent number
US08846705B2

Reaction notes

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