Hydrochloric Acid → (3-Fluoro-4-(4-hydroxypyrimidin-5-yl)pyridin-2-yl)(4-fluorophenyl)methanone

HRID 593763Notes

Reaction equation

HRID 593763 reaction equation
[F:1][C:2]1[C:3]([C:15]#N)=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[C:9]([OH:14])=[N:10][CH:11]=[N:12][CH:13]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([Mg]Br)=[CH:20][CH:19]=1.Cl.[OH-:27].[Na+]>O1CCCC1.C(Cl)Cl.O>[F:1][C:2]1[C:3]([C:15]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=2)=[O:27])=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[C:9]([OH:14])=[N:10][CH:11]=[N:12][CH:13]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 178418676HCID 178418676, compoundHCID 1785105763-Fluoro-4-(4-hydroxypyrimidin-5-yl)picolinonitrile

Product 1

HCID 178519618(3-Fluoro-4-(4-hydroxypyrimidin-5-yl)pyridin-2-yl)(4-fluorophenyl)methanoneYield 73.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-fluoro-4-(4-hydroxypyrimidin-5-yl)picolinonitrile (0.152 g, 0.703 mmol) in tetrahydrofuran (Volume: 2.344 ml) cooled to 0° C. was added (4-fluorophenyl)magnesium bromide (1.055 ml, 2.109 mmol). The reaction mixture was allowed to stir at room temperature overnight. Water and ice were carefully added, followed by acidification with 6 M HCl. After stirring for 1 hr, CH2Cl2 was added and the pH was adjusted to 8.5 with aqueous 4 M NaOH. The layers were separated. The aqueous phase was extracted with CH2Cl2 (5×). Organics combined, dried over Na2SO4, filtered, and concentrated to afford an orange residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (40 g column, 40 mL/min, 0-20% MeOH in CH2Cl2 over 25 min, tr=13 min) gave the title compound (162 mg, 0.517 mmol, 73.5% yield) as a yellow residue. ESI MS (M+H)+=314.1.

Workup

  1. stirringAfter stirring for 1 hr
  2. customThe layers were separated
  3. extractionThe aqueous phase was extracted with CH2Cl2 (5×)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford an orange residue
  8. customto be chromatographed
  9. customPurification of the crude material by silica gel chromatography
  10. customan ISCO machine (40 g column, 40 mL/min, 0-20% MeOH in CH2Cl2 over 25 min, tr=13 min)

Sources & evidence

ORD record
ord-9d549a8f149b422b887173599c9a3bbc
Source dataset
uspto-grants-2016_01
Patent number
US09242967B2

Reaction notes

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