Cyclopropylamine → (R)-6-(5-(cyclopropylamino)-1,3,4-oxadiazol-2-yl)-4-((3,3-dimethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877749Notes

Reaction equation

HRID 877749 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[C:5]([C:8]1[CH:13]=[N:12][N:11]2[CH:14]=[C:15]([C:17]3[O:18][C:19](S(C)=O)=[N:20][N:21]=3)[CH:16]=[C:10]2[C:9]=1[NH:25][C@@H:26]1[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][C:27]1([CH3:40])[CH3:39])(=[O:7])[NH2:6]>>[CH:1]1([NH:4][C:19]2[O:18][C:17]([C:15]3[CH:16]=[C:10]4[C:9]([NH:25][C@@H:26]5[CH2:31][CH2:30][NH:29][CH2:28][C:27]5([CH3:40])[CH3:39])=[C:8]([C:5]([NH2:6])=[O:7])[CH:13]=[N:12][N:11]4[CH:14]=3)=[N:21][N:20]=2)[CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 69828CyclopropylamineHCID 68291350(4R)-tert-butyl 4-((3-carbamoyl-6-(5-(methylsulfinyl)-1,3,4-oxadiazol-2-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-3,3-dimethylpiperidine-1-carboxylate

Product 1

HCID 68291004(R)-6-(5-(cyclopropylamino)-1,3,4-oxadiazol-2-yl)-4-((3,3-dimethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

Procedure

Cyclopropanamine (0.067 mL, 0.966 mmol) was added to a crude solution of (4R)-tert-butyl 4-((3-carbamoyl-6-(5-(methylsulfinyl)-1,3,4-oxadiazol-2-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-3,3-dimethylpiperidine-1-carboxylate (⅙ of the total volume from Step 5, 0.097 mmol maximum). After 22 h at room temperature, the reaction was complete. The mixture was concentrated in vacuo. The crude material was dissolved in dichloromethane (0.5 mL) and treated with trifluoroacetic acid (0.100 mL). After stirring overnight at room temperature, the Boc-deprotection was approximately 50% complete. Additional trifluoroacetic acid (0.185 mL) was added. After 30 min at room temperature, the deprotection was complete. The mixture was concentrated and triturated with ether. The ether layer was decanted. The solid residue was used in the next reaction without purification.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutionThe crude material was dissolved in dichloromethane (0.5 mL)
  3. additiontreated with trifluoroacetic acid (0.100 mL)
  4. additionAdditional trifluoroacetic acid (0.185 mL) was added
  5. waitAfter 30 min at room temperature
  6. concentrationThe mixture was concentrated
  7. customtriturated with ether
  8. customThe ether layer was decanted
  9. customThe solid residue was used in the next reaction without purification

Sources & evidence

ORD record
ord-2a8efa8183484944b0392d9ce2233cb4
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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