Hydrochloric Acid → 2-(1-(1-Methylethyl)-1H-pyrazol-5-yl)-3-pyridinemethanol

HRID 1484780Notes

Reaction equation

HRID 1484780 reaction equation
[Si]([O:8][CH2:9][C:10]1[C:11]([C:16](=O)/[CH:17]=[CH:18]/[N:19](C)C)=[N:12][CH:13]=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.Cl.[CH:24]([NH:27][NH2:28])([CH3:26])[CH3:25].Cl.[CH3:30][CH2:31][OH:32]>>[CH:24]([N:27]1[C:16]([C:11]2[C:10]([CH2:9][OH:8])=[CH:15][CH:14]=[CH:13][N:12]=2)=[CH:17][CH:18]=[N:19]1)([CH3:26])[CH3:25].[CH:24]([N:27]1[CH:14]=[CH:15][C:10]([C:11]2[CH:16]=[CH:17][C:30]([CH2:31][OH:32])=[CH:13][N:12]=2)=[N:28]1)([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 855731-Isopropylhydrazine hydrochlorideHCID 86690729(E)-1-(3-((tert-butyldimethylsilyloxy)methyl)pyridin-2-yl)-3-(dimethylamino)prop-2-en-1-one

Product 2

HCID 89654686(2-(1-isopropyl-1H-pyrazol-3-yl)pyridin-5-yl)methanolYield 25%HCID 896547582-(1-(1-Methylethyl)-1H-pyrazol-5-yl)-3-pyridinemethanolYield 71%

Conditions

Temperature
80 °C

Procedure

To (E)-1-(3-((tert-butyldimethylsilyloxy)methyl)pyridin-2-yl)-3-(dimethylamino)prop-2-en-1-one (crude, 1.03 g, 3.22 mmol, 1 eq.; INT-1) in EtOH (10 mL) was added isopropylhydrazine hydrochloride (430 mg, 3.86 mmol, 1.2 eq.). The mixture was heated at 80° C. for 2 h, cooled, added HCl (6 N, 0.5 mL), and stirred 0/N. The mixture was concentrated and diluted with EtOAc (80 mL) and NaHCO3(sat) (10 mL) solution. The layers were separated and the aqueous layer was extracted with EtOAc three times. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using EtOAc as eluent to give (2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methanol (500 mg, 71%) and (2-(1-isopropyl-1H-pyrazol-3-yl)pyridin-5-yl)methanol (55 mg, 25%) as pale yellow oils. Data for 2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methanol: NMR (400 MHz, CDCl3) δ 8.67 (dd, J=4.7, 1.5 Hz, 1H), 8.0 (d, J=7.8 Hz, 1H), 7.61 (d, J=1.8 Hz, 1H), 7.39 (dd, J=7.8, 4.8 Hz, 1H), 6.37 (d, J=1.8 Hz, 1H), 4.67 (s, 2H), 4.55 (sep, J=6.6 Hz 1H), 1.98-2.05 (br, 1H), 1.47 (d, J=6.6 Hz, 6H). LRMS (M+H+) m/z 218.1 Data for (2-(1-isopropyl-1H-pyrazol-3-yl)pyridin-5-yl)methanol: 1H NMR (400 MHz, CDCl3) δ 8.62 (dd, J=4.8, 1.6 Hz, 1H), 7.72 (d, J=7.6 Hz, 1H), 7.55 (d, J=2.4 Hz, 1H), 7.23 (dd, J=7.6, 4.8 Hz, 1H), 6.99 (dd, J=8.0, 6.5 Hz, 1H), 6.07 (t, J=7.6 Hz, 1H), 4.67 (d, J=7.6 Hz, 2H), 4.58 (sep, J=6.7 Hz, 1H), 1.60 (d, J=6.7 Hz, 1H). MS (ESI) m/z 218.1 [M+H]+.

Workup

  1. temperaturecooled
  2. concentrationThe mixture was concentrated
  3. additiondiluted with EtOAc (80 mL) and NaHCO3(sat) (10 mL) solution
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc three times
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated
  8. custompurified on silica gel

Sources & evidence

ORD record
ord-859ca13a01734e6c9af6aa72ff1b84e2
Source dataset
uspto-grants-2016_08
Patent number
US09422279B2

Reaction notes

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