Diisopropylethylamine → (S)-methyl 2-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)-2-phenylacetate
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.Cl.[NH2:16][C@@H:17]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:18]([O:20][CH3:21])=[O:19].CCN(C(C)C)C(C)C>CN1C(=O)CCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:16][C@@H:17]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:18]([O:20][CH3:21])=[O:19])=[C:8]([C:11](=[O:12])[NH2:13])[CH:7]=[N:6][N:5]2[CH:14]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
6-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Preparation 5, 2.0 g, 7.29 mmol), (S)-methyl 2-amino-2-phenylacetate hydrochloride (2.20 g, 10.93 mmol) and DIPEA (3.82 mL, 21.86 mmol) in NMP (10 mL) were heated in the CEM microwave at 80° C. for 1 hr. The reaction was then quenched with ice-water and the resulting precipitate filtered. The crude solid was purified by column chromatography using hexane:ethyl acetate as eluent to give the title compound (1.32 g, 3.27 mmol, 44.9% yield) as a white solid. HPLC (condition B): retention time=0.93 min. LCMS (condition B): m/z 403.2, 405.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.52 (1 H, d, J=7.48 Hz), 8.31 (1 H, s), 7.88 (1 H, d, J=1.54 Hz), 7.11-7.72 (3H, m), 6.93 (2 H, d, J=1.76 Hz), 6.12 (1 H, d, J=7.70 Hz), 3.31 (3 H, s).
Workup
- customThe reaction was then quenched with ice-water
- filtrationthe resulting precipitate filtered
- customThe crude solid was purified by column chromatography
Sources & evidence
- ORD record
- ord-1a433b12dd8f44f8b7b772ab3f7ca6a1
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09221826B2
Reaction notes
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