Dimethylformamide → HCID 59651871, compound

HRID 2042649Notes

Reaction equation

HRID 2042649 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:14]=[C:13]([O:15][CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH:12]=[CH:11][C:10]=1[C:22]1[CH2:23][CH2:24][C:25](=[O:28])[NH:26][N:27]=1.CN(C)C=O.[C:34]1(=O)[CH2:37][CH2:36][CH2:35]1.C([BH3-])#N.[Na+]>CO.C(Cl)Cl.C([O-])(O)=O.[Na+].C(O)(=O)C>[CH:34]1([N:19]2[CH2:20][CH2:21][CH:16]([O:15][C:13]3[CH:12]=[CH:11][C:10]([C:22]4[CH2:23][CH2:24][C:25](=[O:28])[NH:26][N:27]=4)=[C:9]([F:8])[CH:14]=3)[CH2:17][CH2:18]2)[CH2:37][CH2:36][CH2:35]1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 14496CyclobutanoneHCID 5003444Sodium cyanoborohydrideHCID 67010224HCID 67010224, compound

Product 1

HCID 59651871HCID 59651871, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

In a 25 mL round bottom flask, 6-[2-fluoro-4-(piperidin-4-yloxy)-phenyl]-4,5-dihydro-2H-pyridazin-3-one trifluoroacetic acid salt (420 mg, 1.0 mmol) was dissolved in methanol (10 mL), N,N-dimethylformamide (4 mL), and acetic acid (0.4 mL). Cyclobutanone (0.23 mL, 3.0 mmol), and then sodium cyanoborohydride (0.32 g, 5.0 mmol) were added. The reaction was heated to 60° C. for 2 h. The reaction was cooled and diluted with methylene chloride and NaHCO3 sol. to pH 9. The organics were extracted three times and the solvent concentrated under vacuum. Purification with silica gel chromatography eluting with methylene chloride/methanol (95:5) followed by salt formation with ethereal HCl produced 210 mg (54%). Mp>300° C. MS m/z 346 (M+H).

Workup

  1. temperatureThe reaction was cooled
  2. extractionThe organics were extracted three times
  3. concentrationthe solvent concentrated under vacuum
  4. customPurification with silica gel chromatography
  5. washeluting with methylene chloride/methanol (95:5)
  6. customproduced 210 mg (54%)

Sources & evidence

ORD record
ord-6610d5db403e4978a725980bfa541cb2
Source dataset
uspto-grants-2013_11
Patent number
US08586588B2

Reaction notes

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