Potassium Carbonate → (R)-(4,4-difluoropiperidin-1-yl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone

HRID 1514380Notes

Reaction equation

HRID 1514380 reaction equation
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[C:8]1[N:9]=[N:10][C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=12.[F:24][C:25]1([F:43])[CH2:30][CH2:29][N:28]([C:31](OC2C=CC([N+]([O-])=O)=CC=2)=[O:32])[CH2:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+]>>[F:24][C:25]1([F:43])[CH2:30][CH2:29][N:28]([C:31]([N:6]2[CH2:5][CH2:4][N:3]([C:8]3[N:9]=[N:10][C:11]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[C:12]4[CH:17]=[CH:16][N:15]=[CH:14][C:13]=34)[C@H:2]([CH3:1])[CH2:7]2)=[O:32])[CH2:27][CH2:26]1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 57657605(R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazineHCID 576576134-Nitrophenyl 4,4-difluoropiperidin-1-carboxylate

Product 1

HCID 25227133(R)-(4,4-difluoropiperidin-1-yl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone

Conditions

Temperature
80 °C

Procedure

To a 10 mL round bottomed flask was added (R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazine 16 (110 mg, 360 μmol), 4-nitrophenyl 4,4-difluoropiperidin-1-carboxylate (124 mg, 432 μmol), and potassium carbonate (100 mg, 720 μmol). The reaction was heated to 80° C. overnight. After cooling to room temperature, the solvent was removed under vacuum, and the residue was redissolved in ethyl acetate and washed with water (10 mL), followed by NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Purification by column chromatography afforded (R)-(4,4-difluoropiperidin-1-yl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone 42. MS 452.2 (calc'd) 453.3 (M+H, found).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvent was removed under vacuum
  3. dissolutionthe residue was redissolved in ethyl acetate
  4. washwashed with water (10 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography

Sources & evidence

ORD record
ord-2782ffec105844eb803ff3779f70ae38
Source dataset
uspto-grants-2012_07
Patent number
US08222251B2

Reaction notes

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