Diisopropylethylamine → HCID 68358691, compound

HRID 1408980Notes

Reaction equation

HRID 1408980 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][C@@:4]([CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:7])[C:3]1([CH3:18])[CH3:17].[Br:19][C:20]1[CH:21]=[C:22]2[C:27](Cl)=[C:26]([C:29]([NH2:31])=[O:30])[CH:25]=[N:24][N:23]2[CH:32]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[Br:19][C:20]1[CH:21]=[C:22]2[C:27]([NH:1][C@@H:2]3[CH2:6][CH2:5][C@@:4]([CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:7])[C:3]3([CH3:18])[CH3:17])=[C:26]([C:29](=[O:30])[NH2:31])[CH:25]=[N:24][N:23]2[CH:32]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 682911926-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamideHCID 86707715HCID 86707715, compound

Product 1

HCID 68358691HCID 68358691, compoundYield 72.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of tert-butyl (((1S,3R)-3-amino-1,2,2-trimethylcyclopentyl)methyl)carbamate (417 mg, 1.626 mmol) and 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (446 mg, 1.626 mmol, from preparation 5) in DMF (4.07 ml) was added DIEA (625 μl, 3.58 mmol). The reaction mixture was heated at 90° C. for 2 hrs. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (100 ml). The ethyl acetate solution was washed with water (3×100 ml), dried with sodium sulfate, filtered, and concentrated under reduced pressure, yielding a light yellow oil. The solid was dissolved in 50% EtOAc/hexanes (5 ml) and loaded directly on a pre-packed silica gel column. The crude product was purified via medium pressure chromatography (10-60% EtOAc-hexanes solvent system over 30 minutes) to afford tert-butyl (((1S,3R)-3-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)methyl)carbamate (580 mg, 1.173 mmol, 72.1% yield) as a yellow solid. ESI-MS m/z 496.1 ([M+H]+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe ethyl acetate solution was washed with water (3×100 ml)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customyielding a light yellow oil
  7. customThe crude product was purified via medium pressure chromatography (10-60% EtOAc-hexanes solvent system over 30 minutes)

Sources & evidence

ORD record
ord-3c313d95ac80440da38edf765de4bd4c
Source dataset
uspto-grants-2014_12
Patent number
US08921368B2

Reaction notes

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