Methyl iodide → 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

HRID 1408986Notes

Reaction equation

HRID 1408986 reaction equation
[C:1]([C:4]1[CH:9]=[N:8][N:7]2[CH:10]=[C:11]([C:13]([NH:15][NH2:16])=[O:14])[CH:12]=[C:6]2[C:5]=1[NH:17][C@@H:18]1[CH2:22][CH2:21][C@@:20]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:23])[C:19]1([CH3:33])[CH3:32])(=[O:3])[NH2:2].[C:34](N1C=CN=C1)(N1C=CN=C1)=[S:35].[CH3:46]CN(CC)CC.CI>C1COCC1>[C:1]([C:4]1[CH:9]=[N:8][N:7]2[CH:10]=[C:11]([C:13]3[O:14][C:46]([S:35][CH3:34])=[N:16][N:15]=3)[CH:12]=[C:6]2[C:5]=1[NH:17][C@@H:18]1[CH2:22][CH2:21][C@@:20]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:23])[C:19]1([CH3:33])[CH3:32])(=[O:3])[NH2:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8471TriethylamineHCID 802641,1'-ThiocarbonyldiimidazoleHCID 86707718tert-butyl ((1S,3R)-3-((3-carbamoyl-6-(hydrazinecarbonyl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)carbamate

Product 1

HCID 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)carbamateYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl ((1S,3R)-3-((3-carbamoyl-6-(hydrazinecarbonyl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)carbamate (3.29 g, 7.16 mmol) and 1,1′-thiocarbonyldiimidazole (1.659 g, 9.31 mmol) in THF (25 mL) was heated to 70° C. for 2 hrs. The reaction mixture was added Et3N (2.59 mL, 18.61 mmol) and MeI (0.582 mL, 9.31 mmol) and stirred at RT for 16 hrs which was concentrated and added 150 mL of water which was stirred for 30 minutes. The solid was collected to give the desired 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 (2.35 g, 64% yield). LC/MS (M+H)+=516.3.

Workup

  1. concentrationwas concentrated
  2. additionadded 150 mL of water which
  3. stirringwas stirred for 30 minutes
  4. customThe solid was collected

Sources & evidence

ORD record
ord-ba2a147ece5c43d5828ca2334b35a296
Source dataset
uspto-grants-2014_12
Patent number
US08921368B2

Reaction notes

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