Water → (R)-tert-butyl 4-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)-3,3-dimethylpiperidine-1-carboxylate

HRID 877730Notes

Reaction equation

HRID 877730 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](Cl)=[C:8]([C:11]([NH2:13])=[O:12])[CH:7]=[N:6][N:5]2[CH:14]=1.[NH2:15][C@@H:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][C:17]1([CH3:30])[CH3:29].CCN(C(C)C)C(C)C.O>CC(N(C)C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:15][C@@H:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][C:17]3([CH3:30])[CH3:29])=[C:8]([C:11](=[O:12])[NH2:13])[CH:7]=[N:6][N:5]2[CH:14]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 682911926-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide2×HCID 68945318(R)-Tert-butyl 4-amino-3,3-dimethylpiperidine-1-carboxylate

Product 1

HCID 68291074(R)-tert-butyl 4-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)-3,3-dimethylpiperidine-1-carboxylateYield 54%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 2, 600 mg, 2.186 mmol), (R)-tert-butyl 4-amino-3,3-dimethylpiperidine-1-carboxylate (549 mg, 2.404 mmol) and DIPEA (0.764 mL, 4.37 mmol) in DMA (3.0 mL) was heated at 90° C. for 3 h. The mixture was cooled and added to crushed ice, stirred for 30 min, then extracted with EtOAc (100 mL×3). The combined organic extracts were washed with brine, filtered and concentrated to afford brown oil, which was added to water and stirred for 2 h to afford a solid which was collected by vacuum filtration and dried to afford the title compound as a tan solid (546 mg, 1.17 mmol, 54%). HPLC (Method B) retention time=3.91 min. LCMS (m+1)=466/468(1:1).

Workup

  1. temperatureThe mixture was cooled
  2. additionadded
  3. customto crushed ice
  4. extractionextracted with EtOAc (100 mL×3)
  5. washThe combined organic extracts were washed with brine
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford brown oil, which
  9. stirringstirred for 2 h
  10. customto afford a solid which
  11. filtrationwas collected by vacuum filtration
  12. customdried

Sources & evidence

ORD record
ord-10d6034148b6488d9812dd410758e8fb
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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