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

HRID 877720Notes

Reaction equation

HRID 877720 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][CH: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].C(N(CC)C(C)C)(C)C.CN(C)C=O>O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:15][CH: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 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 10171391Tert-butyl 4-amino-3,3-dimethylpiperidine-1-carboxylateHCID 682911926-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide2×

Product 1

HCID 68290809Tert-butyl 4-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)-3,3-dimethylpiperidine-1-carboxylateYield 67%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (310 mg, 1.129 mmol, Intermediate 2), tert-butyl 4-amino-3,3-dimethylpiperidine-1-carboxylate (387 mg), N,N-diisopropylethylamine (0.592 mL, 3.39 mmol) and N,N-dimethylformamide (2 mL) was pumped under vacuum and backfiled with nitrogen twice. The reaction vial was sealed and heated to 90° C. for 2 h. The mixture was diluted with water (20 mL) and extracted with ethyl acetate twice. The organic layer was washed with brine and concentrated. Silica gel chromatography, eluting with 0-60% ethyl acetate in hexanes, gave the title compound as a brown solid (0.3510 g, 67% yield). MS (ES+) m/z: 466.1, 468.1 (M+H); LC retention time: 4.488 min (analytical HPLC Method H).

Workup

  1. customThe reaction
  2. customvial was sealed
  3. extractionextracted with ethyl acetate twice
  4. washThe organic layer was washed with brine
  5. concentrationconcentrated
  6. washSilica gel chromatography, eluting with 0-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-01230035d9464eecaabee903fc3bdcb2
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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