Azetidine → HCID 178428241, compound

HRID 1042088Notes

Reaction equation

[Cl:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[N:19]=[C:18](Cl)[CH:17]=[C:16]([NH:21][C:22]3[NH:23][N:24]=[C:25]([CH3:27])[CH:26]=3)[N:15]=2)=[CH:9][CH:8]=1)=[O:5].[NH:32]1[CH2:35][CH2:34][CH2:33]1.C(N(CC)C(C)C)(C)C>C(O)CCC>[N:32]1([C:18]2[CH:17]=[C:16]([NH:21][C:22]3[NH:23][N:24]=[C:25]([CH3:27])[CH:26]=3)[N:15]=[C:14]([S:13][C:10]3[CH:9]=[CH:8][C:7]([NH:6][C:4](=[O:5])[C:3]4[CH:28]=[CH:29][CH:30]=[CH:31][C:2]=4[Cl:1])=[CH:12][CH:11]=3)[N:19]=2)[CH2:35][CH2:34][CH2:33]1

Participants

Conditions

Temperature: 90 °C

Procedure

A 500 mL round bottom flask was charged with 2-chloro-N-{4-[4-chloro-6-(5-methyl-2H-pyrazol-3-ylamino)-pyrimidin-2-ylsulfanyl]-phenyl}-benzamide (16.0 g, 34.0 mmol), azetidine (3.87 g, 68.0 mmol), N,N-diisopropylethylamine (13.0 mL, 74.7 mmol) and n-butanol (250 mL). The reaction mixture was stirred at 90° C. for 5 h. The reaction mixture was cooled and concentrated in vacuo. Diethyl ether (200 mL) was added and a light brown solid precipitated. The solution was filtered and the solid recrystallized from ethanol to give the pure product as a white solid (9.42 g, 52%) 1H NMR (DMSO): 2.04 (3H, s), 2.32 (2H, m), 3.87 (4H, m), 5.39 (1H, s), 5.66 (1H, br s), 7.48-7.59 (6H, m), 7.82 (2H, m), 9.87 (1H, s), 10.74 (1H, s), 11.68 (1H, s); MS (ES+): 492.

Workup

temperatureThe reaction mixture was cooled
concentrationconcentrated in vacuo
additionDiethyl ether (200 mL) was added
customa light brown solid precipitated
filtrationThe solution was filtered
customthe solid recrystallized from ethanol

Sources & evidence

ORD record: ord-99739a9b300f4e4ba718806ccdb13eb9
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08557833B2

Reaction notes

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