Diisobutylaluminumhydride → (1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazol-4-yl)methanol

HRID 539894Notes

Reaction equation

HRID 539894 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH:12]=[C:11]([C:13](OCC)=[O:14])[C:10]([CH3:18])=[N:9]2)[CH:5]=[CH:4][N:3]=1.CC1C(CN2CC(O)C2)=CN(C2C=CN=C(NC3C=C4C(=CC=3)N(C)C=C4)N=2)N=1.[H-].C([Al+]CC(C)C)C(C)C>O1CCCC1.C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH:12]=[C:11]([CH2:13][OH:14])[C:10]([CH3:18])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 21225700DiisobutylaluminumhydrideHCID 716983751-((3-methyl-1-(2-(1-methyl-1H-indol-5-ylamino)pyrimidin-4-yl)-1H-pyrazol-4-yl)methyl)azetidin-3-olHCID 86698981ethyl 1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carboxylate

Product 1

HCID 86698984(1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazol-4-yl)methanolYield 66%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carboxylate intermediate 1 (6.5 g, 24.0 mmol) in 50 mL of anhydrous tetrahydrofuran (THF), was slowly added 109 mL (4.5 equiv.) of 1M solution of di-isobutylaluminum hydride (DIBAL-H) in toluene with ice bath cooling. After being stirred for 2 hours at room temperature, the reaction was quenched by slow addition of 1N—NaOH solution. It was diluted with ethyl acetate and washed with brine. The collected organic layer was dried over anhydrous sodium sulfate and then partially concentrated in vacuo. To this, was heptane added to form pale yellow precipitates. The resulting solids were collected by filtration and rinsed with heptanes and then dried under high vacuum to give 3.6 g (66%) of intermediate alcohol 6. MS (ESI) m/z 225 [M+H]+.

Workup

  1. temperaturecooling
  2. customthe reaction was quenched by slow addition of 1N—NaOH solution
  3. additionIt was diluted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe collected organic layer was dried over anhydrous sodium sulfate
  6. concentrationpartially concentrated in vacuo
  7. additionadded
  8. customto form pale yellow precipitates
  9. filtrationThe resulting solids were collected by filtration
  10. washrinsed with heptanes
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-1b9eb75bbf984c6baac6f4ec2dfaa682
Source dataset
uspto-grants-2014_10
Patent number
US08871778B2

Reaction notes

Loading…