(Diethylamino)sulfur trifluoride → 4-[6-bromo-3-(fluoromethyl)-1H-indazol-1-yl]pyrimidin-2-amine

HRID 1398609Notes

Reaction equation

HRID 1398609 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([Br:17])[CH:15]=3)[C:10]([CH2:18]O)=[N:9]2)[CH:5]=[CH:4][N:3]=1.C(N(S(F)(F)[F:26])CC)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Br:17][C:14]1[CH:15]=[C:16]2[C:11]([C:10]([CH2:18][F:26])=[N:9][N:8]2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[N:7]=2)=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 68181849[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-indazol-3-yl]methanol

Product 1

HCID 681818784-[6-bromo-3-(fluoromethyl)-1H-indazol-1-yl]pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [1-(2-aminopyrimidin-4-yl)-6-bromo-1H-indazol-3-yl]methanol (200 mg, 0.47 mmol) in dry DCM (10 mL) at RT under an atmosphere of nitrogen was introduced (diethylamino)sulphur trifluoride (0.08 mL, 0.63 mmol). After 16 hr at this temperature, the reaction mixture was treated with sodium bicarbonate (25 mL of saturated aq NaHCO3) and extracted with DCM (2×20 mL extractions). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (Biotage, heptane/EtOAc gradient) to furnish the title compound as a colorless solid: 1H NMR (500 MHz, DMSO) delta 5.86 (2H, d, J=48.24 Hz), 7.06 (1H, d, J=5.04 Hz), 7.14 (2H, br. s.), 7.58 (1H, dd, J=8.04, 2.05 Hz), 7.92 (1H, d, J=8.98 Hz), 8.31 (1H, d, J=6.31 Hz), 9.17 (1H, d, J=1.42 Hz); LC-MS: m/z=+321.90/323.90 (M+H)+.

Workup

  1. extractionextracted with DCM (2×20 mL extractions)
  2. dry with materialThe combined organic extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (Biotage, heptane/EtOAc gradient)

Sources & evidence

ORD record
ord-eec66b80fdd546ad8c90c1fe0f0269d4
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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