Potassium hydroxy sulfite → tert-butyl ((1S,3R)-3-((3-carbamoyl-6-(5-(methylsulfinyl)-1,3,4-oxadiazol-2-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)carbamate

HRID 1408987Notes

Reaction equation

HRID 1408987 reaction equation
[C:1]([C:4]1[CH:9]=[N:8][N:7]2[CH:10]=[C:11]([C:13]3[O:14][C:15]([S:18][CH3:19])=[N:16][N:17]=3)[CH:12]=[C:6]2[C:5]=1[NH:20][C@@H:21]1[CH2:25][CH2:24][C@@:23]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:26])[C:22]1([CH3:36])[CH3:35])(=[O:3])[NH2:2].[OH:37]OS([O-])=O.[K+]>CC(C)=O.O.CCOC(C)=O>[C:1]([C:4]1[CH:9]=[N:8][N:7]2[CH:10]=[C:11]([C:13]3[O:14][C:15]([S:18]([CH3:19])=[O:37])=[N:16][N:17]=3)[CH:12]=[C:6]2[C:5]=1[NH:20][C@@H:21]1[CH2:25][CH2:24][C@@:23]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:26])[C:22]1([CH3:36])[CH3:35])(=[O:3])[NH2:2]

Participants

6

Reactant 2

HCID 23707502Potassium hydroxy sulfiteHCID 86707719tert-butyl ((1S,3R)-3-((3-carbamoyl-6-(5-(methylthio)-1,3,4-oxadiazol-2-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)carbamate

Product 1

HCID 86707720tert-butyl ((1S,3R)-3-((3-carbamoyl-6-(5-(methylsulfinyl)-1,3,4-oxadiazol-2-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)carbamateYield 23%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl ((1S,3R)-3-((3-carbamoyl-6-(5-(methylthio)-1,3,4-oxadiazol-2-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)carbamate (805 mg, 1.561 mmol) in acetone (16 mL) was added oxone (1.920 g, 3.12 mmol) in water (16.00 mL) and stirred for 2 hrs. The reaction mixture was diluted with 150 mL of EtOAc which was washed with 50 mL of 10% LiCl solution, 50 mL of brine and dried over Na2SO4. Filtration and concentration yielded a crude product which was purified on silica gel column with EtOAc to give tert-butyl ((1S,3R)-3-((3-carbamoyl-6-(5-(methylsulfinyl)-1,3,4-oxadiazol-2-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)carbamate (186.6 mg, 23% yield). HPLC retention time=2.993 min. LC-MS: M+1 532.3. 1H-NMR (400 MHz, methanol-d4) δ 8.30 (d, J=1.8 Hz, 1H), 8.26 (s, 1H), 7.51 (d, J=1.8 Hz, 1H), 4.50 (d, J=9.0 Hz, 1H), 3.31 (s, 3H, under MeOH peak), 2.51-2.32 (m, 1H), 2.29-2.13 (m, 1H), 2.12-1.95 (m, 1H), 1.83-1.63 (m, 1H), 1.49 (s, 3H), 1.46 (s, 9H), 1.13 (s, 3H), 1.09 (s, 3H).

Workup

  1. washwas washed with 50 mL of 10% LiCl solution, 50 mL of brine
  2. dry with materialdried over Na2SO4
  3. filtrationFiltration and concentration
  4. customyielded a crude product which
  5. customwas purified on silica gel column with EtOAc

Sources & evidence

ORD record
ord-e0838c2275984ab18cf52b098eec8ca5
Source dataset
uspto-grants-2014_12
Patent number
US08921368B2

Reaction notes

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