2-Aminothiophenol → HCID 178420811, compound

HRID 1846811Notes

Reaction equation

HRID 1846811 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:8]([O:13][CH:14]3[CH2:17][CH:16]([C:18](O)=O)[CH2:15]3)=[N:9][CH:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[SH:34].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[O:1]1[CH2:2][CH2:3][CH:4]([C:7]2[C:8]([O:13][C@H:14]3[CH2:15][C@H:16]([C:18]4[S:34][C:29]5[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=5[N:27]=4)[CH2:17]3)=[N:9][CH:10]=[CH:11][CH:12]=2)[CH2:5][CH2:6]1.[O:1]1[CH2:2][CH2:3][CH:4]([C:7]2[C:8]([O:13][C@@H:14]3[CH2:15][C@H:16]([C:18]4[S:34][C:29]5[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=5[N:27]=4)[CH2:17]3)=[N:9][CH:10]=[CH:11][CH:12]=2)[CH2:5][CH2:6]1

Participants

9

Reactant 4

HCID 87132-AminothiophenolHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 58548534HCID 58548534, compound

Product 2

HCID 178420811HCID 178420811, compoundYield 9%HCID 178420812HCID 178420812, compoundYield 6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)cyclobutanecarboxylic acid (prepared according to Scheme 4) (0.236 g, 0.851 mmol) in DCM (0.5 mL) at RT was added DMF (1 drop) and oxalyl dichloride (0.50 mL, 5.6 mmol). The reaction mixture was stirred at RT for 10 min and the solvent was removed under reduced pressure. The concentrate was dissolved in toluene (3 mL), cooled to 0° C., and 2-aminobenzenethiol (0.10 mL, 0.94 mmol) was added. The reaction mixture was warmed to RT and stirred for 2 h. The reaction was neutralized with saturated NaHCO3 and diluted with EtOAc. The organic phase was washed with water (1×), brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes) followed by purification by flash column chromatography on silica gel (5% to 30% DCM in hexanes) gave 2-(trans-3-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)cyclobutyl)benzo[d]thiazole (0.018 g, 0.049 mmol, 6% yield) and 2-(cis-3-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)cyclobutyl)benzo[d]thiazole (0.029 g, 0.079 mmol, 9% yield) as colorless oils. [M+1]=367 each. IC50 (uM): 0.01497 (trans) and 0.0633 (cis).

Workup

  1. customthe solvent was removed under reduced pressure
  2. dissolutionThe concentrate was dissolved in toluene (3 mL)
  3. temperaturecooled to 0° C.
  4. temperatureThe reaction mixture was warmed to RT
  5. stirringstirred for 2 h
  6. washThe organic phase was washed with water (1×), brine (1×)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes)
  11. customfollowed by purification by flash column chromatography on silica gel (5% to 30% DCM in hexanes)

Sources & evidence

ORD record
ord-3b98dda9ac5c4f45888a5db65f17b9ba
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

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