Sodium hydride → HCID 178505994, compound

HRID 1846796Notes

Reaction equation

HRID 1846796 reaction equation
[H-].[Na+].[S:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[NH:12][C@@H:13]1[CH2:16][C@H:15](O)[CH2:14]1.F[C:19]1[C:24]([CH:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[CH:23][C:22]([F:31])=[CH:21][N:20]=1.[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[S:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[NH:12][C@H:13]1[CH2:16][C@H:15]([C:19]2[C:24]([CH:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)=[CH:23][C:22]([F:31])=[CH:21][N:20]=2)[CH2:14]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 585485232,5-Difluoro-3-(tetrahydro-pyran-4-YL)-pyridineHCID 178521635HCID 178521635, compound

Product 1

HCID 178505994HCID 178505994, compoundYield 11.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (81.8 mg, 2.0 mmol) was added to a solution of cis-3-(benzothiazol-2-ylamino)-cyclobutanol (150 mg, 0.68 mmol) in DMF (3 mL) under argon and the mixture was stirred for 1 h at RT. Then 2,5-difluoro-3-(tetrahydro-pyran-4-yl)-pyridine (162 mg, 0.82 mmol) was added and the mixture was heated to 100° C. for 2 h. It was cooled to RT and EtOAc (25 mL) and saturated NH4Cl (15 mL) were added. The organic layer was separated, washed with water (2×25 mL), brine (25 mL), dried over MgSO4, filtered and concentrated in vacuo to give an oil, which was purified by prep-HPLC to give trans-benzothiazol-2-yl-{3-[5-fluoro-3-(tetrahydro-pyran-4-yl)-pyridin-2-yl]-cyclobutyl}-amine (30 mg, yield 10%). [M+1] 400. IC50 (uM) 0.0001.

Workup

  1. temperaturethe mixture was heated to 100° C. for 2 h
  2. temperatureIt was cooled to RT
  3. customThe organic layer was separated
  4. washwashed with water (2×25 mL), brine (25 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give an oil, which
  9. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-2be73c0088e24bd6bc58f4213a709e63
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

Loading…