Triethylamine → (R)-(3-methyl-4-(1-phenylpyrido[4,3-d]pyridazin-4-yl)piperazin-1-yl)(tetrahydro-2H-pyran-4-yl)methanone

HRID 1514375Notes

Reaction equation

HRID 1514375 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.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C.[O:52]1[CH2:57][CH2:56][CH:55]([C:58](O)=[O:59])[CH2:54][CH2:53]1.C([O-])(O)=O.[Na+]>ClCCl.C(OCC)(=O)C>[CH3:1][C@H:2]1[N:3]([C:8]2[C:13]3[CH:14]=[N:15][CH:16]=[CH:17][C:12]=3[C:11]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[N:10][N:9]=2)[CH2:4][CH2:5][N:6]([C:58]([CH:55]2[CH2:56][CH2:57][O:52][CH2:53][CH2:54]2)=[O:59])[CH2:7]1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 219302Oxane-4-carboxylic acidHCID 516892Sodium BicarbonateHCID 57657605(R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazine

Product 1

HCID 25226765(R)-(3-methyl-4-(1-phenylpyrido[4,3-d]pyridazin-4-yl)piperazin-1-yl)(tetrahydro-2H-pyran-4-yl)methanone

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[4,3-d]pyridazine 16 (125 mg, 409 μmol) in dichloromethane (5 mL) was added HOBT (3.1 mg, 20 μmol), EDCI (86 mg, 450 μmol), triethylamine (114 μl, 819 μmol), and tetrahydro-2H-pyran-4-carboxylic acid (64 mg, 491 μmol). After 1 hour, 10 mL of sat NaHCO3 and 100 mL of ethyl acetate were added. The layers were separated and the organic layer was washed with 1×10 mL of brine, dried over MgSO4, filtered, and concentrated. Purified by column chromatography (hexanes:acetone) to isolate (R)-(3-methyl-4-(1-phenylpyrido[4,3-d]pyridazin-4-yl)piperazin-1-yl)(tetrahydro-2H-pyran-4-yl)methanone 30. MS: 417.2 (calc'd) 418.1 (M+H, found).

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with 1×10 mL of brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurified by column chromatography (hexanes:acetone)

Sources & evidence

ORD record
ord-541013da3de34f3393b79f8a2a11665e
Source dataset
uspto-grants-2012_07
Patent number
US08222251B2

Reaction notes

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