Sodium hydride → 4-[3-((2S,6R)-2,6-Dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-cyclohexylamine

HRID 2200044Notes

Reaction equation

HRID 2200044 reaction equation
[H-].[Na+].[NH2:3][C@H:4]1[CH2:9][CH2:8][C@H:7]([OH:10])[CH2:6][CH2:5]1.[CH3:11][C@H:12]1[CH2:17][CH2:16][CH2:15][C@@H:14]([CH3:18])[N:13]1[C:19]1[N:23]2[CH:24]=[C:25](F)[CH:26]=[CH:27][C:22]2=[N:21][N:20]=1>CN(C=O)C>[CH3:11][C@H:12]1[CH2:17][CH2:16][CH2:15][C@@H:14]([CH3:18])[N:13]1[C:19]1[N:23]2[CH:24]=[C:25]([O:10][CH:7]3[CH2:8][CH2:9][CH:4]([NH2:3])[CH2:5][CH2:6]3)[CH:26]=[CH:27][C:22]2=[N:21][N:20]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 896242853-(cis-2,6-Dimethyl-piperidin-1-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridineHCID 178511715HCID 178511715, compound

Product 1

HCID 1177290354-[3-((2S,6R)-2,6-Dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-cyclohexylamineYield 88.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60% in mineral oil, 0.24 g, 6.00 mmol) was added to a stirred solution of trans-4-amino cyclohexanol (0.24 g, 2.08 mmol) in anhydrous DMF (8 mL) at RT under an argon atmosphere. The reaction mixture was stirred at RT for 30 min, then Intermediate 3c (0.50 g, 2.01 mmol) in anhydrous DMF (7 mL) was added and stirred at 60° C. for 4 h. After cooling, the reaction mixture was quenched by careful addition of a saturated aqueous solution of NH4Cl and water (1:1) and extracted with DCM (3×50 mL). The combined organic layers were washed with water followed by brine, dried and concentrated in vacuo. The resultant residue was purified by FCC using 0-10% [2M NH3 in MeOH] in DCM to afford the title compound (0.61 g, 88%) as a brown oil. LCMS (Method 3): Rt 2.19 min, m/z 344 [MH+].

Workup

  1. stirringstirred at 60° C. for 4 h
  2. temperatureAfter cooling
  3. customthe reaction mixture was quenched by careful addition of a saturated aqueous solution of NH4Cl and water (1:1)
  4. extractionextracted with DCM (3×50 mL)
  5. washThe combined organic layers were washed with water
  6. customdried
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was purified by FCC

Sources & evidence

ORD record
ord-3d65340a8fdd45d1aced53f527578879
Source dataset
uspto-grants-2016_06
Patent number
US09359354B2

Reaction notes

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