tert-butyl (5-methyl-1,3,4-thiadiazol-2-yl)methyl(2-methyl-6-(((1S,2S)-2-(5-methyl pyridin-2-yl)cyclopropyl)methoxy)-3-oxo-2,3-dihydropyridazin-4-yl)carbamate → 2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)methylamino)-6-(((1S,2S)-2-(5-methyl pyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one

HRID 530790Notes

Reaction equation

HRID 530790 reaction equation
[CH3:1][C:2]1[S:6][C:5]([CH2:7][N:8]([C:16]2[C:17](=[O:35])[N:18]([CH3:34])[N:19]=[C:20]([O:22][CH2:23][C@H:24]3[CH2:26][C@@H:25]3[C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][N:28]=3)[CH:21]=2)C(=O)OC(C)(C)C)=[N:4][N:3]=1>C(O)(C(F)(F)F)=O>[CH3:34][N:18]1[C:17](=[O:35])[C:16]([NH:8][CH2:7][C:5]2[S:6][C:2]([CH3:1])=[N:3][N:4]=2)=[CH:21][C:20]([O:22][CH2:23][C@H:24]2[CH2:26][C@@H:25]2[C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][N:28]=2)=[N:19]1

Participants

3

Reactant 1

HCID 131735649tert-butyl (5-methyl-1,3,4-thiadiazol-2-yl)methyl(2-methyl-6-(((1S,2S)-2-(5-methyl pyridin-2-yl)cyclopropyl)methoxy)-3-oxo-2,3-dihydropyridazin-4-yl)carbamate

Product 1

HCID 904543862-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)methylamino)-6-(((1S,2S)-2-(5-methyl pyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl (5-methyl-1,3,4-thiadiazol-2-yl)methyl(2-methyl-6-(((1S,2S)-2-(5-methyl pyridin-2-yl)cyclopropyl)methoxy)-3-oxo-2,3-dihydropyridazin-4-yl)carbamate (7) (95 mg, 0.19 mmol) in TFA (1 mL) was stirred at room temperature for 1 h. The reaction mixture was concentrated and 10 mL sat. aq. NaHCO3 was added, extracted with EA (3×10 mL). The organic phase was dried with anhydrous Na2SO4, filtered and concentrated. The residue was purified by Prep-TLC using PE/EtOAc=1/2 to give title compound as a oil. 1H NMR (400 MHz, DMSO) δ 8.23 (s, 1H), 7.55 (t, 1H), 7.45 (d, 1H), 7.18 (d, 1H), 5.86 (s, 1H), 4.73-4.71 (m, 2H), 4.09-4.04 (m, 1H), 3.97-3.97 (m, 1H), 3.51 (s, 3H), 2.66 (s, 3H), 2.22 (s, 3H), 2.11-2.05 (m, 1H), 1.72-1.68 (m, 1H), 1.14-1.09 (m, 1H), 0.99-0.94 (m, 1H); LRMS m/z (M+H) 399.2 found, 399.15 required.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. addition10 mL sat. aq. NaHCO3 was added
  3. extractionextracted with EA (3×10 mL)
  4. dry with materialThe organic phase was dried with anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by Prep-TLC

Sources & evidence

ORD record
ord-ba0022f6869642399e3ca4db2173e69d
Source dataset
uspto-grants-2016_05
Patent number
US09353104B2

Reaction notes

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