Triethylamine → 6-Fluoro-3-(4-methyl-4-triisopropylsilanyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine

HRID 630814Notes

Reaction equation

HRID 630814 reaction equation
FC(F)(F)S([O:6][Si:7]([CH:14]([CH3:16])[CH3:15])([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:10])[CH3:9])(=O)=O.[F:19][C:20]1[CH:21]=[CH:22][C:23]2[N:24]([C:26]([N:29]3[CH2:34][CH2:33][C:32]([CH3:36])(O)[CH2:31][CH2:30]3)=[N:27][N:28]=2)[CH:25]=1.CCN(CC)CC>C(Cl)Cl>[F:19][C:20]1[CH:21]=[CH:22][C:23]2[N:24]([C:26]([N:29]3[CH2:34][CH2:33][C:32]([CH3:36])([O:6][Si:7]([CH:8]([CH3:9])[CH3:10])([CH:11]([CH3:12])[CH3:13])[CH:14]([CH3:15])[CH3:16])[CH2:31][CH2:30]3)=[N:27][N:28]=2)[CH:25]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2724529Triisopropylsilyl trifluoromethanesulfonateHCID 866870971-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-methyl-piperidin-4-ol

Product 1

HCID 866870986-Fluoro-3-(4-methyl-4-triisopropylsilanyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridineYield 96.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Triisopropylsilyl trifluoromethanesulfonate (550 mg, 1.81 mmol) was added to a solution of Intermediate 79c (150 mg, 0.60 mmol) and Et3N (242 mg, 2.40 mmol) in a DCM (5 mL) and the mixture stirred at reflux for 1 h. The reaction mixture was diluted with DCM (30 mL), washed with water (2×), brine, dried (MgSO4), and then concentrated in vacuo. The residue was purified by FCC, using 0-10% MeOH in DCM, to give the title compound (235 mg, 96%). 1H NMR (400 MHz, CDCl3): 1.00-1.20 (21H, m), 1.40 (3H, s), 1.76-1.93 (4H, m), 3.18-3.29 (2H, m), 3.44-3.58 (2H, m), 7.03-7.12 (1H, m), 7.58-7.69 (2H, m).

Workup

  1. temperatureat reflux for 1 h
  2. washwashed with water (2×), brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-c81a4fafa07647f8889826ec07f54412
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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