HCID 86690766, compound → HCID 86690765, compound

HRID 1471722Notes

Reaction equation

HRID 1471722 reaction equation
[CH3:1][Mg]Br.[O:4]1[CH2:8][CH2:7][O:6][CH:5]1[C:9]1[CH:14]=[C:13]([O:15][CH3:16])[N:12]=[CH:11][C:10]=1[O:17][CH2:18][C:19]1[C:20]([C:25](=[O:28])[CH2:26]C)=[N:21][CH:22]=[CH:23][CH:24]=1>C1COCC1>[O:6]1[CH2:7][CH2:8][O:4][CH:5]1[C:9]1[CH:14]=[C:13]([O:15][CH3:16])[N:12]=[CH:11][C:10]=1[O:17][CH2:18][C:19]1[C:20]([C:25]([OH:28])([CH3:1])[CH3:26])=[N:21][CH:22]=[CH:23][CH:24]=1

Participants

4

Reactant 2

HCID 86690766HCID 86690766, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 86690765HCID 86690765, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methylmagnesium bromide (3M/ether, 0.25 mL, 0.75 mmol, 3.0 eq.) was added to a stirred solution of 1-(3-((4-(1,3-dioxolan-2-yl)-6-methoxypyridin-3-yloxy)methyl)pyridin-2-yl)propan-1-one (82 mg, 0.25 mmol, 1 eq.) in THF (5.0 mL) at −78° C. After addition, the reaction mixture was warm to rt and quenched with aqueous citric acid solution. The aqueous layer was extracted with EtOAc (20 mL) twice. The combined organic layers were washed with NaHCO3(sat) solution and brine, dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 2-(3-((4-(1,3-dioxolan-2-yl)-6-methoxypyridin-3-yloxy)methyl)pyridin-2-yl)propan-2-ol (38 mg, 44%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.43 (dd, J=7.7, 1.6 Hz, 1H), 7.84 (dd, J=7.7, 1.5 Hz, 1H), 7.74 (s, 1H), 7.18 (dd, J=7.7, 4.7 Hz, 1H), 6.84 (s, 1H), 6.01 (s, 1H), 5.27 (s, 2H), 4.07-3.88 (m, 4H), 3.82 (s, 3H), 1.55 (s, 6H). LRMS (M+H+) m/z 347.1.

Workup

  1. additionAfter addition
  2. customquenched with aqueous citric acid solution
  3. extractionThe aqueous layer was extracted with EtOAc (20 mL) twice
  4. washThe combined organic layers were washed with NaHCO3(sat) solution and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. custompurified on silica gel using
  8. additiona mixture of EtOAc and hexanes as eluent

Sources & evidence

ORD record
ord-55b70a72a9dd4a90acddb78a199c9d0a
Source dataset
uspto-grants-2015_04
Patent number
US09012450B2

Reaction notes

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