Dichloromethane → HCID 178461981, compound

HRID 42349Notes

Reaction equation

HRID 42349 reaction equation
C([NH:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([C@H:15]([NH:17][C:18]2[N:19]=[C:20]([OH:35])[C:21]3[N:27]=[C:26]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[CH:25]=[CH:24][C:22]=3[N:23]=2)[CH3:16])=[CH:11][CH:10]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.ClCCl.C([O-])(O)=O.[Na+]>CCOC(C)=O>[F:34][C:31]1[CH:30]=[CH:29][C:28]([C:26]2[CH:25]=[CH:24][C:22]3[N:23]=[C:18]([NH:17][C@@H:15]([C:12]4[CH:13]=[CH:14][C:9]([S:6]([NH2:5])(=[O:7])=[O:8])=[CH:10][CH:11]=4)[CH3:16])[N:19]=[C:20]([OH:35])[C:21]=3[N:27]=2)=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 178461982HCID 178461982, compound

Product 1

HCID 178461981HCID 178461981, compoundYield 55.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of crude (R)—N-tert-butyl-4-(1-(6-(4-fluorophenyl)-4-hydroxypyrido[3,2-d]pyrimidin-2-ylamino)ethyl)benzenesulfonamide (670 mg), TFA (5 ml) and dichloromethane (1 ml) was stirred at room temperature overnight. Solvents were removed under vacuum. To the residue was added a mixture of acetonitrile (5 ml) and water (50 ml) with vigorous stirring whereupon some oily material was formed. The mixture was diluted by EtOAc, neutralized by adding sat. aq. NaHCO3 and extracted with EtOAc. The organic layer was dried and concentrated. The residue was dissolved in EtOAc (40 ml) and dichloromethane (20 ml) was added slowly, followed by hexanes (5 ml). The resulting solid was collected to give 328 mg (R)-4-(1-(6-(4-fluorophenyl)-4-hydroxypyrido[3,2-d]pyrimidin-2-ylamino)ethyl)benzenesulfonamide. The filtrate was concentrated and purified by reverse phase HPLC (eluting by ACN/H2O+0.1% TFA) to give 200 mg (R)-4-(1-(6-(4-fluorophenyl)-4-hydroxypyrido[3,2-d]pyrimidin-2-ylamino)ethyl)benzenesulfonamide.

Workup

  1. customSolvents were removed under vacuum
  2. additionTo the residue was added
  3. additiona mixture of acetonitrile (5 ml) and water (50 ml)
  4. stirringwith vigorous stirring whereupon some oily material
  5. customwas formed
  6. extractionextracted with EtOAc
  7. customThe organic layer was dried
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in EtOAc (40 ml)
  10. additiondichloromethane (20 ml) was added slowly
  11. customThe resulting solid was collected

Sources & evidence

ORD record
ord-692c02bdb3484ce597eb6b3f825c26fc
Source dataset
uspto-grants-2013_09
Patent number
US08536187B2

Reaction notes

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