Methanol → HCID 59810846, compound

HRID 2113728Notes

Reaction equation

HRID 2113728 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[CH:11]1([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:23]4[N:27]([C:28]5[CH:37]=[CH:36][C:31]([C:32](OC)=[O:33])=[CH:30][CH:29]=5)[N:26]=[CH:25][CH:24]=4)[CH:21]=3)[C:16]([CH2:38][CH3:39])=[N:15]2)[CH2:13][CH2:12]1.CO.C(OCC)(=O)C>C1(C)C=CC=CC=1.O1CCCC1.O>[CH:11]1([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:23]4[N:27]([C:28]5[CH:29]=[CH:30][C:31]([CH2:32][OH:33])=[CH:36][CH:37]=5)[N:26]=[CH:25][CH:24]=4)[CH:21]=3)[C:16]([CH2:38][CH3:39])=[N:15]2)[CH2:13][CH2:12]1

Participants

8

Reactant 4

HCID 887MethanolHCID 8857Ethyl AcetateHCID 21225700DiisobutylaluminumhydrideHCID 68712506HCID 68712506, compound

Product 1

HCID 59810846HCID 59810846, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of diisobutylaluminum hydride (0.19 mL, 1.5 M in toluene, 0.28 mmol) in toluene (0.19 mL) was added dropwise to a solution of methyl 4-[5-(1-cyclopropyl-3-ethyl-1H-indazol-6-yl)-1H-pyrazol-1-yl]benzoate (36 mg, 0.093 mmol) in tetrahydrofuran (5 mL) under an atmosphere of argon at −78° C. The reaction was allowed to warm to room temperature over a period of 1 hour. The mixture was then chilled to −40° C. and methanol (4 mL) was slowly added. Again, the reaction was allowed to warm slowly to room temperature, then it was poured into a mixture of ethyl acetate and water. The product was extracted (3×ethyl acetate), and the combined organics were dried and concentrated. The residue was purified by silica gel column chromatography using 50% ethyl acetate in hexanes as the eluent to afford 22.6 mg (68%) of 4-[5-(1-cyclopropyl-3-ethyl-1H-indazol-6-yl)-1H-pyrazol-1-yl]phenyl}methanol. LC/MS (EI) tR 3.19 (Method A), m/z 359.2 (M++1). 1H NMR (CDCl3) δ 1.0 (m, 4H); 1.2 (t, 3H); 2.5 (m, 1H); 2.8 (m, 2H); 3.2 (m, 1H); 4.5 (s, 2H); 6.5 (s, 1H); 6.9 (t, 1H); 7.0-7.2 (m, 5H); 7.5 (d, 1H); 7.6 (s, 1H).

Workup

  1. temperatureThe mixture was then chilled to −40° C.
  2. temperatureto warm slowly to room temperature
  3. extractionThe product was extracted (3×ethyl acetate)
  4. customthe combined organics were dried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography
  7. customto afford 22.6 mg (68%) of 4-[5-(1-cyclopropyl-3-ethyl-1H-indazol-6-yl)-1H-pyrazol-1-yl]phenyl}methanol

Sources & evidence

ORD record
ord-2d1fc58993a44dcd89d5e089a0810d1d
Source dataset
uspto-grants-2008_10
Patent number
US07432266B2

Reaction notes

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