Dimethylamine → (S)-1,1-dimethyl-3-(3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)urea

HRID 521572Notes

Reaction equation

HRID 521572 reaction equation
[CH3:1][N:2]([C@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[C:3]1[CH:4]=[C:5]([NH2:13])[C:6]2[N:7]([C:9]([CH3:12])=[N:10][N:11]=2)[N:8]=1.[C:22](Cl)(=[O:30])OC1C=CC=CC=1.[CH3:32][NH:33][CH3:34]>C(Cl)Cl.C1COCC1.O>[CH3:32][N:33]([CH3:34])[C:22]([NH:13][C:5]1[C:6]2[N:7]([C:9]([CH3:12])=[N:10][N:11]=2)[N:8]=[C:3]([N:2]([CH3:1])[C@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[CH:4]=1)=[O:30]

Participants

7

Reactant 3

HCID 674DimethylamineHCID 15891Phenyl chloroformateHCID 71498805(S)-N6, 3-dimethyl-N6-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazine-6,8-diamine

Product 1

HCID 71115972(S)-1,1-dimethyl-3-(3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)ureaYield 16.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of compound (S)-N6, 3-dimethyl-N6-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazine-6,8-diamine (50 mg, 0.17 mmol) in DCM (10 mL) was added phenyl carbonochloridate (30 mg, 0.19 mmol) dropwise at 0° C. The reaction mixture was stirred at room temperature for 1 h and then the solution of dimethylamine in THF (0.3 mL, 1 N) was added, and the mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water (15 mL) and extracted with EA (20 mL*3). The combined organic layers were dried over Na2SO4, concentrated in vacuum. The residue was purified by prep-TLC (DCM: MeOH=20:1) to give product (S)-1,1-dimethyl-3-(3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)urea (Compound 8) as a yellow solid (10 mg, 16.7%). 1H NMR (300 MHz, CDCl3) δ 7.96 (s, 1H), 7.80 (s, 1H), 7.34-7.32 (m, 5H), 3.12 (s, 6H), 2.80 (s, 3H), 2.65 (s, 3H), 1.60 (d, 3H); LRMS (M+H+) m/z: calcd 353.20; found 353.

Workup

  1. stirringthe mixture was stirred at room temperature for 2 h
  2. extractionextracted with EA (20 mL*3)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated in vacuum
  5. customThe residue was purified by prep-TLC (DCM: MeOH=20:1)

Sources & evidence

ORD record
ord-6eaf1dfb626245b6a05642b5a53e9ef4
Source dataset
uspto-grants-2016_05
Patent number
US09328117B2

Reaction notes

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