Methanol → HCID 57489647, compound

HRID 2044096Notes

Reaction equation

HRID 2044096 reaction equation
[F:1][C:2]1[C:3]([C:24]2[CH2:29][CH2:28][CH2:27][C:26](=O)[CH:25]=2)=[N:4][C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:14][CH:13]=2)=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8].C([O-])(=O)C.[NH4+:35].[BH4-].[Na+].CO>CN(C=O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[NH2:35][CH:26]1[CH2:27][CH2:28][CH2:29][C:24]([C:3]2[C:2]([F:1])=[CH:10][C:6]([C:7]([NH2:9])=[O:8])=[C:5]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[CH:14][CH:13]=3)[N:4]=2)=[CH:25]1

Participants

7

Reactant 4

HCID 887MethanolHCID 517165Ammonium AcetateHCID 4311764Sodium borohydrideHCID 57489644HCID 57489644, compound

Product 1

HCID 57489647HCID 57489647, compoundYield 8.7%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 5-fluoro-2-(4-morpholinophenylamino)-6-(3-oxocyclohex-1-enyl)nicotinamide (1.2 g, 2.92 mmol), ammonium acetate (2.254 g, 29.2 mmol) and titanium(IV) isopropoxide (2.57 mL, 8.77 mmol) in DMF (0.8 mL) was stirred at rt overnight. To the above solution were added sodium borohydride (0.221 g, 5.85 mmol) and 0.2 mL of MeOH. Violent bubbling occurred and the reaction mixture became warm. The reaction mixture was stirred at rt for 1 h. To the reaction mixture was added 1N NaOH (10 mL). A precipitate formed and was filtered through CELITE®, washed with a mixture of methylene chloride, and MeOH (50% each cosolvent) many times until the filter cake was white. The filtrate was washed with water; the aqueous fraction was back extracted 3 times with methylene chloride. The combined organic fractions were concentrated and the residue was purified by MPLC (ISCO, 5%-20% gradient ammonia/methanol/methylene chloride, 40 g silica gel column) to yield 105 mg of product as a yellow solid.

Workup

  1. customViolent bubbling
  2. temperaturethe reaction mixture became warm
  3. additionTo the reaction mixture was added 1N NaOH (10 mL)
  4. customA precipitate formed
  5. filtrationwas filtered through CELITE®
  6. washwashed with a mixture of methylene chloride, and MeOH (50% each cosolvent) many times until the filter cake
  7. washThe filtrate was washed with water
  8. extractionthe aqueous fraction was back extracted 3 times with methylene chloride
  9. concentrationThe combined organic fractions were concentrated
  10. customthe residue was purified by MPLC (ISCO, 5%-20% gradient ammonia/methanol/methylene chloride, 40 g silica gel column)

Sources & evidence

ORD record
ord-dc4b3d510578419f84870906be12e96c
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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