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

HRID 1484780ノート

反応式

HRID 1484780 の反応式
[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]

参加物

6

反応物 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

生成物 2

HCID 89654686(2-(1-isopropyl-1H-pyrazol-3-yl)pyridin-5-yl)methanol収率 25%HCID 896547582-(1-(1-Methylethyl)-1H-pyrazol-5-yl)-3-pyridinemethanol収率 71%

反応条件

温度
80 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-859ca13a01734e6c9af6aa72ff1b84e2
出典データセット
uspto-grants-2016_08
特許番号
US09422279B2

反応ノート

読み込み中…