tert-Butanol → (S)-tert-butyl 3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazin-8-ylcarbamate

HRID 521569Notes

Reaction equation

HRID 521569 reaction equation
C1C=CC(P([N:15]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[CH3:18][C:19]([OH:22])([CH3:21])[CH3:20].[CH3:23][C:24]1[N:28]2[N:29]=[C:30]([N:36]([CH3:45])[C@H:37]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH3:38])[CH:31]=[C:32](C(O)=O)[C:27]2=[N:26][N:25]=1.[O:46]1[CH2:51]COCC1>>[C:19]([O:22][C:51](=[O:46])[NH:15][C:32]1[C:27]2[N:28]([C:24]([CH3:23])=[N:25][N:26]=2)[N:29]=[C:30]([N:36]([CH3:45])[C@H:37]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH3:38])[CH:31]=1)([CH3:21])([CH3:20])[CH3:18]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 312751,4-DioxaneHCID 199401P,P-Diphenylphosphinic azideHCID 71115949(S)-3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylic acid

Product 1

HCID 71115937(S)-tert-butyl 3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazin-8-ylcarbamateYield 24.5%

Procedure

A mixture of DPPA (264 mg, 0.96 mmol), t-BuOH (1.0 mL), TEA (0.96 mmol), (S)-3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylic acid (200 mg, 0.64 mmol) in anhydrous 1,4-dioxane (10 mL) was heated to reflux and stirred for overnight. The mixture was quenched with water (40 mL) and extracted with EA (30 mL*3). The combined organic layers were washed with brine (50 mL), dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash column chromatography (silica-gel, DCM: MeOH=10:1) to give product (S)-tert-butyl3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazin-8-ylcarbamate as a yellow oil (60 mg, 24.5%). 1H NMR (300 MHz, CDCl3) δ: 7.55 (s, 1H), 7.29˜7.34 (m, 5H), 5.81˜5.83 (s, 1H), 2.81 (s, 3H), 2.66 (s, 3H), 1.61 (d, 3H, J=6.9 Hz), 1.54 (s, 9H). LRMS (M+H+) m/z: calcd 383; found 383.

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. customThe mixture was quenched with water (40 mL)
  4. extractionextracted with EA (30 mL*3)
  5. washThe combined organic layers were washed with brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuum
  8. customThe residue was purified by flash column chromatography (silica-gel, DCM: MeOH=10:1)

Sources & evidence

ORD record
ord-f7e4714e6a9b40bd857f889043897a3f
Source dataset
uspto-grants-2016_05
Patent number
US09328117B2

Reaction notes

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