Hydrochloric Acid → HCID 67131516, compound

HRID 1926717Notes

Reaction equation

HRID 1926717 reaction equation
[CH:1]1([C:4]2[N:9]=[CH:8][C:7]([O:10][C:11]3[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=3)=[CH:6][N:5]=2)[CH2:3][CH2:2]1.[CH3:19][NH2:20].C1COCC1.[BH4-].[Na+].[ClH:28]>CC#N.CCOC(C)=O>[ClH:28].[ClH:28].[CH:1]1([C:4]2[N:9]=[CH:8][C:7]([O:10][C:11]3[CH:18]=[CH:17][C:14]([CH2:15][CH2:19][NH2:20])=[CH:13][CH:12]=3)=[CH:6][N:5]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6329MethylamineHCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 86623130HCID 86623130, compound

Product 1

HCID 67131516HCID 67131516, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 4-[(2-cyclopropylpyrimidin-5-yl)oxy]benzaldehyde (0.240 g, 1.0 mmol) in MeCN (0.50 mL) was added 2M methylamine in THF (2.0 mL, 4.0 mmol) followed by sodium borohydride (0.120 g, 3.2 mmol) and MeCN (0.50 mL). The slurry was stirred for 30 minutes. The solvents were removed by evaporation, water was added and the mixture was extracted with EtOAc. The organic phase was washed with brine and evaporated onto silica gel. This gel was applied onto a 20 g silica gel column. Column chromatography using a gradient of 10% to 60% EtOAc in heptanes eluted impurities. Elution with 10% MeOH in EtOAc (100 mL) followed by 5% concentrated NH3 in MeOH (100 mL) gave the product in the basic fractions. These fractions were combined, concentrated and re-dissolved in water. The pH was adjusted to 13 to 14 using sodium hydroxide solution and the mixture was extracted several times with EtOAc. The organic extracts were washed with brine, dried over potassium carbonate, filtered and concentrated to give an oily residue. This oil was dissolved in EtOAc and an excess of a 1.5M solution of hydrogen chloride in EtOAc was added. The solvent was removed by evaporation to give 0.186 g (56% yield) of the crude subtitle compound. The salt obtained was 93.9% pure and was used without further purification.

Workup

  1. customThe solvents were removed by evaporation, water
  2. additionwas added
  3. extractionthe mixture was extracted with EtOAc
  4. washThe organic phase was washed with brine
  5. customevaporated onto silica gel
  6. washElution with 10% MeOH in EtOAc (100 mL)
  7. customgave the product in the basic fractions
  8. concentrationconcentrated
  9. dissolutionre-dissolved in water
  10. extractionthe mixture was extracted several times with EtOAc
  11. washThe organic extracts were washed with brine
  12. dry with materialdried over potassium carbonate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto give an oily residue
  16. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-b3d6f672954d4c159f3ef546a71a110c
Source dataset
uspto-grants-2012_05
Patent number
US08183251B2

Reaction notes

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