Sodium hydride → HCID 178420807, compound

HRID 1846780Notes

Reaction equation

HRID 1846780 reaction equation
F[C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[S:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=[C:15]1[CH:23]1[CH2:28][CH2:27][CH:26]([OH:29])[CH2:25][CH2:24]1.[H-].[Na+]>CC(N(C)C)=O.O>[O:11]1[CH2:12][CH2:13][CH:8]([C:7]2[C:2]([O:29][C@H:26]3[CH2:25][CH2:24][C@H:23]([C:15]4[S:14][C:18]5[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=5[N:16]=4)[CH2:28][CH2:27]3)=[N:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][CH2:10]1.[O:11]1[CH2:12][CH2:13][CH:8]([C:7]2[C:2]([O:29][C@@H:26]3[CH2:25][CH2:24][C@H:23]([C:15]4[S:14][C:18]5[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=5[N:16]=4)[CH2:28][CH2:27]3)=[N:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][CH2:10]1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 58548620HCID 58548620, compoundHCID 593271552-Fluoro-3-(tetrahydro-2H-pyran-4-yl)pyridine

Product 2

HCID 178420807HCID 178420807, compoundYield 3.5%HCID 178420808HCID 178420808, compoundYield 3.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-fluoro-3-(tetrahydro-pyran-4-yl)-pyridine, as prepared in preparation 1a, (200 mg, 1.1 mmol), 4-benzothiazol-2-yl-cyclohexanol (257 mg, 1.1 mmol) and NaH (60%) (53 mg, 2.2 mmol) in DMA (4 mL) was heated to 120° C. for 2 h. Then the reaction mixture was diluted with water (10 mL) and extracted with EtOAc (3×15 mL), washed with brine, dried over Na2SO4. After concentration, the residue was purified by Prep-TLC and then Prep-HPLC to give trans-2-{4-[3-(Tetrahydro-pyran-4-yl)-pyridin-2-yloxy]-cyclohexyl}-benzothiazole (14 mg, 0.036 mmol, 3.2% yield) and cis-2-{4-[3-(Tetrahydro-pyran-4-yl)-pyridin-2-yloxy]-cyclohexyl}-benzothiazole (15 mg, 0.038 mmol, 3.5%). [M+1] 395 each. IC50 (uM): (trans) 0.408 and (cis) 0.584.

Workup

  1. extractionextracted with EtOAc (3×15 mL)
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationAfter concentration
  5. customthe residue was purified by Prep-TLC

Sources & evidence

ORD record
ord-7341b1a1afb0478fbac765e6a26338cb
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

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