Dichloromethane → (S)-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-3-carbonitrile

HRID 521579Notes

Reaction equation

HRID 521579 reaction equation
[CH3:1][N:2]([C@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16])[C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([C:12]([NH2:14])=O)=[N:10][N:11]=2)[N:8]=1.C([O-])(O)=O.[Na+].C(Cl)Cl>CN(C=O)C.O=S(Cl)Cl>[CH3:1][N:2]([C@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16])[C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([C:12]#[N:14])=[N:10][N:11]=2)[N:8]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 71115968(S)-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxamide

Product 1

HCID 71116017(S)-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 24386Thionyl ChlorideSolvent

Procedure

To a solution of compound (S)-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxamide (0.1 g, 0.34 mmol) in 2 mL of DMF, 1 mL of SOCl2 was added dropwise at 0-5° C., the reaction mixture was stirred for 5 h at room temperature. The mixture was poured onto ice (20 mL) and the mixture was neutralized with NaHCO3. DCM (50 mL) was added; the separated organic layer was dried over anhydrous Na2SO4, and concentrated in vacuum. The residue was purified by flash chromatography eluting with PE/EA=5:1 to give product (S)-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-3-carbonitrile as a yellow solid (Compound 9) (60 mg, 64%). LRMS (M+H+) m/z: calcd 279.43; found 279. 1H NMR (300 MHz, CDCl3): δ 7.98-7.94 (d, J=12 Hz, 1H), 7.35-7.30 (m, 5H), 7.11-7.08 (d, J=9 Hz, 1H), 5.77-5.75 (q, 1H), 2.94 (s, 3H), 1.69-1.66 (d, 3H).

Workup

  1. additionThe mixture was poured onto ice (20 mL)
  2. dry with materialthe separated organic layer was dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuum
  4. customThe residue was purified by flash chromatography
  5. washeluting with PE/EA=5:1

Sources & evidence

ORD record
ord-bb53633afe4a475a9a78908f9e51392b
Source dataset
uspto-grants-2016_05
Patent number
US09328117B2

Reaction notes

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