Water → Benzyl 4-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-3,3-dimethylpyrrolidine-1-carboxylate

HRID 877808Notes

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[CH2:20][N:19]([C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[CH2:18][C:17]1([CH3:32])[CH3:31].O>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:15][CH:16]3[CH2:20][N:19]([C:21]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:22])[CH2:18][C:17]3([CH3:32])[CH3:31])=[C:8]([C:11](=[O:12])[NH2:13])[CH:7]=[N:6][N:5]2[CH:14]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A solution of 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 2, 63.0 mg, 0.230 mmol) in N,N-dimethylformamide (0.5 mL), was added benzyl 4-amino-3,3-dimethylpyrrolidine-1-carboxylate (Intermediate 11, 57 mg, 0.230 mmol) and N,N-diiospropylethylamine (0.121 mL), and heated at 90° C. for 16 h. The reaction was added water, stirred at rt for a 3 hours and filtered. The solid was rinsed with water and dried under vacuum to give benzyl 4-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-3,3-dimethylpyrrolidine-1-carboxylate (72 mg, 64.5% yield) as a yellow solid. 1H NMR (400 MHz, METHANOL-d4) δ 10.83-10.77 (m, 1H), 8.16 (s, 1H), 7.67 (s, 1H), 7.41-7.27 (m, 7H), 7.09-7.04 (m, 1H), 5.18-5.08 (m, 2H), 4.56-4.45 (m, 1H), 4.16-3.95 (m, 1H), 3.42 (d, J=2.2 Hz, 3H), 1.20 (d, J=13.9 Hz, 6H); MS (ES+) m/z: 486.4, 487.9 (M+H); LC retention time: 4.02 min (analytical HPLC Method I).

Workup

filtrationfiltered
washThe solid was rinsed with water
customdried under vacuum

Sources & evidence

ORD record: ord-755f64504ed0434eb6091929024dc8f6
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987268B2

Reaction notes

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