(3,3,3-Trifluoropropyl)hydrazine dihydrochloride → 3-((tert-butyldimethylsilyloxy)methyl)-2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridine

HRID 1484767Notes

Reaction equation

HRID 1484767 reaction equation
[Si:1]([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:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.Cl.[F:25][C:26]([F:32])([F:31])[CH2:27][CH2:28][NH:29]N>CCO>[Si:1]([O:8][CH2:9][C:10]1[C:11]([C:16]2[N:29]([CH2:28][CH2:27][C:26]([F:32])([F:31])[F:25])[N:19]=[CH:18][CH:17]=2)=[N:12][CH:13]=[CH:14][CH:15]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 86690726(3,3,3-Trifluoropropyl)hydrazine dihydrochlorideHCID 86690729(E)-1-(3-((tert-butyldimethylsilyloxy)methyl)pyridin-2-yl)-3-(dimethylamino)prop-2-en-1-one

Product 1

HCID 866907283-((tert-butyldimethylsilyloxy)methyl)-2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridineYield 76%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To (E)-1-(3-((tert-butyldimethylsilyloxy)methyl)pyridin-2-yl)-3-(dimethylamino)prop-2-en-1-one (crude above, 1.73 g, 5.41 mmol, 1 eq.) in EtOH (10 mL) was added (3,3,3-trifluoropropyl)hydrazine dihydrochloride (1.30 g, crude above, 6.49 mmol, 1.2 eq.) at RT. The mixture was heated at 80° C. for 1 h, concentrated, and diluted with EtOAc (50 mL) and NaHCO3(sat) solution (10 mL). The layers were separated and aqueous layer was extracted with EtOAc three times. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 3-((tert-butyldimethylsilyloxy)methyl)-2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridine (1.58 g; 76% for 2 steps). 1H NMR (400 MHz, CDCl3) δ 8.53 (dd, J=4.7, 1.6 Hz, 1H), 7.96-7.88 (m, 1H), 7.51 (d, J=1.9 Hz, 1H), 7.29 (dd, J=7.9, 4.7 Hz, 1H), 6.34 (d, J=1.9 Hz, 1H), 4.62 (s, 2H), 4.45-4.33 (m, 2H), 2.82-2.61 (m, 2H), 0.85 (s, 8H), −0.00 (s, 5H). MS (ESI) m/z 386.2 [M+H]+.

Workup

  1. concentrationconcentrated
  2. additiondiluted with EtOAc (50 mL) and NaHCO3(sat) solution (10 mL)
  3. customThe layers were separated
  4. extractionaqueous layer was extracted with EtOAc three times
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated
  7. custompurified on silica gel using
  8. additiona mixture of EtOAc and hexanes as eluent

Sources & evidence

ORD record
ord-6eeaf8f0276347a4a7ddc4f7fff8b7e3
Source dataset
uspto-grants-2016_08
Patent number
US09422279B2

Reaction notes

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