Aluminium lithium hydride → [1-(2-aminopyrimidin-4-yl)-6-bromo-1H-indazol-3-yl]methanol

HRID 1398608Notes

Reaction equation

HRID 1398608 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]([C:18](OCC)=[O:19])=[N:9]2)[CH:5]=[CH:4][N:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[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][OH:19])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 68181670ethyl 1-(2-aminopyrimidin-4-yl)-6-bromo-1H-indazole-3-carboxylate

Product 1

HCID 68181849[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-indazol-3-yl]methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution ethyl 1-(2-aminopyrimidin-4-yl)-6-bromo-1H-indazole-3-carboxylate (500 mg, 0.88 mmol) in dry THF (4 mL) at 0° C. under an atmosphere of nitrogen was introduced lithium aluminium hydride (3.5 mL of a 1M solution in THF, 3.50 mmol). After 10 minutes at this temperature, the reaction mixture was quenched by carefully transferring into a rapidly stirred saturated aqueous solution of Rochelle's salt (5 mL). The suspension was extracted with DCM (10 mL) and the organic extract filtered through a pad of Celite®. The filtrate was washed with water (5 mL) and brine (5 mL), dried (Na2SO4), filtered and the filtrate concentrated in vacuo to furnish the crude title compound as a colorless solid: 1H NMR (250 MHz, DMSO) delta 4.84 (2H, d, J=5.48 Hz), 5.61 (1H, t, J=5.71 Hz), 7.04 (3H, s), 7.51 (1H, dd, J=8.45, 1.75 Hz), 7.92 (1H, d, J=8.53 Hz), 8.28 (1H, d, J=5.48 Hz), 9.11 (1H, d, J=1.22 Hz); LC-MS: m/z=+319.90/321.80 (M+H)+. This compound, with LC-MS purity=76% UV, was used in the next step without further purification.

Workup

  1. customthe reaction mixture was quenched
  2. extractionThe suspension was extracted with DCM (10 mL)
  3. extractionthe organic extract
  4. filtrationfiltered through a pad of Celite®
  5. washThe filtrate was washed with water (5 mL) and brine (5 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-613ee22a9c3d4c279d6802385c5654a5
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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