Sodium Bicarbonate → 4-Fluoro-5-(4-fluorobut-1-yn-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1254437Notes

Reaction equation

HRID 1254437 reaction equation
[F:1][C:2]1[C:10]([C:11]#[C:12][CH2:13][CH2:14]O)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][O:17]1.[B-](F)(F)(F)[F:23].CCN([S+](F)F)CC.C([O-])(O)=O.[Na+]>ClCCl>[F:1][C:2]1[C:10]([C:11]#[C:12][CH2:13][CH2:14][F:23])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][O:17]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 44517918(Diethylamino)(difluoro)sulfanium tetrafluoroborateHCID 66793278HCID 66793278, compound2×

Product 1

HCID 667931834-Fluoro-5-(4-fluorobut-1-yn-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 37.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-3-yn-1-ol (3.4 g, 11.8 mmol; Intermediate 29, Step 1) in dry dichloromethane (100 mL), was added triethylamine-3HF (7.6 g, 47.2 mmol). XtalFluor-E (8.0 g, 34.9 mmol) was then added. The resulting solution was stirred at room temperature for 30 minutes. Upon completion, the reaction solution was neutralized by slow addition of saturated NaHCO3 (30 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0˜20% EtOAc in petroleum ether), and then re-crystallized from petroleum ether to afford the title compound (1.3 g). 1H NMR (300 MHz, DMSO-d6): δ 8.27 (s, 1H), 7.58 (d, 1H), 7.44 (dd, 1H), 5.89 (dd, 1H), 4.60 (dt, 2H), 3.91-3.85 (m, 1H), 3.80-3.69 (m, 1H), 2.93 (dt, 2H), 2.46-2.28 (m, 1H), 2.06-1.95 (m, 2H), 1.78-1.67 (m, 1H), 1.60-1.52 (m, 2H); LCMS: 291 (M+H)+.

Workup

  1. dry with materialThe organic layer was dried over Na2SO4
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (0˜20% EtOAc in petroleum ether)
  4. customre-crystallized from petroleum ether

Sources & evidence

ORD record
ord-d0334e60fb50419cb75469c81f38b009
Source dataset
uspto-grants-2013_06
Patent number
US08455534B2

Reaction notes

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