Water → 6-bromo-4-((3R,4S)-1-(5-cyanopyrimidin-2-yl)-4-methoxypyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877826Notes

Reaction equation

I.[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([O:17][CH3:18])[CH2:15][NH:14][CH2:13]3)=[C:9]([C:19]([NH2:21])=[O:20])[CH:8]=[N:7][N:6]2[CH:22]=1.CS[C:25]1[N:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][N:26]=1.C(N(CC)C(C)C)(C)C.O>CN(C)C=O>[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([O:17][CH3:18])[CH2:15][N:14]([C:25]4[N:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][N:26]=4)[CH2:13]3)=[C:9]([C:19]([NH2:21])=[O:20])[CH:8]=[N:7][N:6]2[CH:22]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 6-bromo-4-(((3R,4S)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide (from Step 2 of Example 302, 200 mg, 0.415 mmol) in N,N-dimethylformamide (1 mL), was added 2-(methylthio)pyrimidine-5-carbonitrile (75 mg, 0.5 mmol) and N,N-diisopropylethylamine (0.22 mL, 1.25 mmol). The mixture was heated at 80° C. for 5 h. The mixture was added water, stirred at rt for 2 h, filtered and rinsed with water to give 6-bromo-4-((3R,4S)-1-(5-cyanopyrimidin-2-yl)-4-methoxypyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide (162 mg, 80% yield). 1H NMR (400 MHz, METHANOL-d4) δ 8.38 (d, J=2.0 Hz, 1H), 8.17 (s, 1H), 7.73 (dd, J=8.9, 2.3 Hz, 1H), 7.10 (s, 1H), 6.59 (s, 1H), 5.10-5.01 (m, 1H), 4.25 (d, J=3.7 Hz, 1H), 4.09 (br. s., 1H), 3.85-3.74 (m, 2H), 3.61-3.46 (m, 5H), 1.28 (d, J=6.4 Hz, 2H); MS (ES+) m/z: 372.26 (M+H); LC retention time: 1.92 min (analytical HPLC Method H).

Workup

filtrationfiltered
washrinsed with water

Sources & evidence

ORD record: ord-f74844f7064c457ebffc207bf0b9a932
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987268B2

Reaction notes

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