Water → 5-(4-Chlorobut-1-yn-1-yl)-4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1254436Notes

Reaction equation

HRID 1254436 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.O=P(Cl)(Cl)[Cl:24].O>N1C=CC=CC=1>[Cl:24][CH2:14][CH2:13][C:12]#[C:11][C:10]1[C:2]([F:1])=[C:3]2[C:7](=[CH:8][CH:9]=1)[N:6]([CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][O:17]1)[N:5]=[CH:4]2

Participants

5

Reactant 3

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 66793278HCID 66793278, compound

Product 1

HCID 667931255-(4-Chlorobut-1-yn-1-yl)-4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 53.4%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a mixture of 4-(4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-3-yn-1-ol (4.6 g, 16.0 mmol) in pyridine (50 mL), was added POCl3 (10.3 g, 67.3 mmol). The resulting solution was stirred at room temperature for 2 hours. Upon completion, the reaction solution was poured into water (250 mL) and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified on silica gel column (0˜10% EtOAc in petroleum ether) affording the title compound (2.62 g). 1H NMR (300 MHz, DMSO-d6): δ 8.13 (s, 1H), 7.58 (d, 1H), 7.43 (dd, 1H), 5.87 (dd, 1H), 3.90-3.69 (m, 2H), 3.83 (t, 2H), 2.98 (t, 1H), 2.41-2.29 (m, 1H), 2.06-1.94 (m, 2H), 1.78-1.70 (m, 1H), 1.60-1.54 (m, 2H); LCMS: 307 (M+H)+.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified on silica gel column (0˜10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-b75fa948337645d98789c926c02214f8
Source dataset
uspto-grants-2013_06
Patent number
US08455534B2

Reaction notes

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