Aluminium lithium hydride → 1-[2-(4-Hydroxymethyl-phenyl)-5-isopropyl-2h-pyrazol-3-yl]-3-naphthalen-1-yl-urea

HRID 492021Notes

Reaction equation

HRID 492021 reaction equation
C([O:3][C:4](=O)[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15]([NH:16][C:17]([NH:19][C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=[CH:22][CH:21]=3)=[O:18])=[CH:14][C:13]([C:30](C)([CH3:32])[CH3:31])=[N:12]2)=[CH:7][CH:6]=1)C.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15]([NH:16][C:17]([NH:19][C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=[CH:22][CH:21]=3)=[O:18])=[CH:14][C:13]([CH:30]([CH3:32])[CH3:31])=[N:12]2)=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 588428904-[3-t-Butyl-5-(3-naphthalen-1-yl-ureido)-pyrazol-1-yl]-benzoic acid ethyl ester

Product 1

HCID 184498271-[2-(4-Hydroxymethyl-phenyl)-5-isopropyl-2h-pyrazol-3-yl]-3-naphthalen-1-yl-ureaYield 124.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of Example 195 (500 mg, 0.83 mmol) in THF (10 mL) was added LiAlH4 powder (65 mg, 1.66 mmol) in portion at 0° C. under N2. The mixture was stirred for 2 h at RT, excess LiAlH4 was destroyed by a slow addition of ice, and the reaction mixture was acidified to pH=7 with dilute HCl. After the solvent was removed, the residue was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), and filtered. After concentration in vacuo, the crude product was purified by preparative-TLC to afford 1-[2-(4-hydroxymethyl-phenyl)-5-isopropyl-2H-pyrazol-3-yl]-3-naphthalen-1-yl-urea (415 mg, 92%). 1H NMR (DMSO-d6): 9.04 (s, 1H), 8.78 (s, 1H), 7.98 (d, J=8.0 Hz, 1H), 7.90 (d, J=7.2 Hz, 2H), 7.63 (d, J=8.4 Hz, 1H), 7.55-7.42 (m, 7H), 6.39 (s, 1H), 5.30 (t, J=5.6 Hz, 1H), 4.56 (d, J=5.6 Hz, 2H), 1.27 (s, 9H); MS (ESI) m/z: 415 (M+H+).

Workup

  1. customexcess LiAlH4 was destroyed by a slow addition of ice
  2. customAfter the solvent was removed
  3. extractionthe residue was extracted with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationAfter concentration in vacuo
  8. customthe crude product was purified by preparative-TLC

Sources & evidence

ORD record
ord-b33c645f0be04c3482a5c0435174a537
Source dataset
uspto-grants-2009_05
Patent number
US07531566B2

Reaction notes

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