Acetic Acid → 6-chloro-4-(5-(1-isopropylpiperidin-4-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

HRID 1431113Notes

Reaction equation

HRID 1431113 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[CH3:23][C:24]([CH3:26])=O.C([BH3-])#N.[Na+].C(O)(=O)C>CO.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH:24]([CH3:26])[CH3:23])[CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 180Acetone2×HCID 5003444Sodium cyanoborohydride2×HCID 667421406-chloro-2-methyl-4-(5-(piperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

Product 1

HCID 667433416-chloro-4-(5-(1-isopropylpiperidin-4-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-oneYield 97.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-chloro-2-methyl-4-(5-(piperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-one (200 mg, 625 μmol, Eq: 1.00) and acetone (799 mg, 1.01 ml, 13.8 mmol, Eq: 22) in MeOH (5 ml) was added sodium cyanoborohydride (39.3 mg, 625 μmol, Eq: 1.00) and acetic acid (656 mg, 625 μl, 10.9 mmol, Eq: 17.5). The reaction mixture stirred under N2 for 18 h. Additional acetone (1 ml) was added, followed by THF (3 ml). The reaction mixture continued stirring under N2 for 2 h. Additional sodium cyanoborohydride (19.7 mg, 313 μmol, Eq: 0.50) was added. The mixture stirred for 4 h. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 50% to 100% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give 6-chloro-4-(5-(1-isopropylpiperidin-4-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one (220 mg, 97%). LC/MS-ESI observed [M+H]+ 362.

Workup

  1. stirringThe reaction mixture continued stirring under N2 for 2 h
  2. stirringThe mixture stirred for 4 h
  3. concentrationConcentrated in vacuo
  4. customThe crude material was purified by flash chromatography (silica gel, 12 g, 50% to 100% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient)

Sources & evidence

ORD record
ord-cf2e55bf0c1e430f8ab8127d6cdc0b93
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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