2-Mercaptoethanol → HCID 23654508, compound

HRID 661049Notes

Reaction equation

HRID 661049 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][C@H:9]([NH:30]S(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)[CH2:10][N:11]([C:15]2[S:16][C:17]([C:20]3[CH:21]=[C:22]4[C:27](=[CH:28][CH:29]=3)[CH:26]=[N:25][CH:24]=[CH:23]4)=[CH:18][N:19]=2)C(=O)C)[CH:5]=[CH:6][CH:7]=1.[OH-].[Na+].SCCO.C([O-])([O-])=O.[K+].[K+]>CCO.[NH4+].[Cl-].O.C(Cl)Cl.CN(C=O)C>[NH2:30][C@@H:9]([CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)[CH2:10][NH:11][C:15]1[S:16][C:17]([C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[CH:26]=[N:25][CH:24]=[CH:23]3)=[CH:18][N:19]=1

Participants

10

Reactant 4

HCID 15672-MercaptoethanolHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 68993235HCID 68993235, compound

Product 1

HCID 23654508HCID 23654508, compoundYield 15.7%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 25517Ammonium ChlorideSolvent2×

Conditions

Temperature
80 °C

Procedure

To a stirred mixture of crude N—((S)-3-(3-chlorophenyl)-2-(4-nitrophenylsulfonamido)propyl)-N-(5-(isoquinolin-6-yl)thiazol-2-yl)acetamide (0.33 g, 0.535 mmol) in EtOH (3 mL), was added sodium hydroxide (1.1 mL, 1 M aqueous solution, 1.1 mmol) at room temperature. After addition, the reaction mixture was stirred at 80° C. overnight. The reaction mixture was then diluted with NH4Cl (10 mL (aqueous)) and water (10 mL), and diluted with DCM (5 mL). The separated aqueous layer was extracted with EtOAc (5 mL×2), and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give the crude residue (0.2233 g, 385 μmol), to which DMF (2 mL), 2-mercaptoethanol (60 mg, 770 μmol), and K2CO3 (160 mg, 1155 μmol) were added sequentially. The resulting mixture was stirred at room temperature for 1.5 hours, and the resulting dark mixture was diluted with NH4Cl (5 mL (aqueous)) and water (5 mL) and diluted with DCM (5 mL). The separated aqueous layer was extracted with DCM (10 mL×2), and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give the crude residue which was purified with flash column chromatography (pure DCM→5% MeOH in DCM) to obtain the desired product N—((S)-2-amino-3-(3-chlorophenyl)propyl)-5-(isoquinolin-6-yl)thiazol-2-amine (33 mg, 84 μmol) as a yellow solid.

Workup

  1. additionAfter addition
  2. extractionThe separated aqueous layer was extracted with EtOAc (5 mL×2)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto give the crude residue (0.2233 g, 385 μmol)
  7. stirringThe resulting mixture was stirred at room temperature for 1.5 hours
  8. extractionThe separated aqueous layer was extracted with DCM (10 mL×2)
  9. washthe combined organic layers were washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customto give the crude residue which
  13. customwas purified with flash column chromatography (pure DCM→5% MeOH in DCM)

Sources & evidence

ORD record
ord-b5a8d0e1c0dc4056b4d6e72c788965de
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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