Ethanolamine → 1-{5-[6-(2-Hydroxy-ethylamino)-imidazo[1,2-b]pyridazin-3-yl]-thiophen-2-yl}-ethanone

HRID 870621Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].F[C:8]1[CH:9]=[CH:10][C:11]2[N:12]([C:14]([C:17]3[S:21][C:20]([C:22](=[O:24])[CH3:23])=[CH:19][CH:18]=3)=[CH:15][N:16]=2)[N:13]=1.[CH2:25]([CH2:27][NH2:28])[OH:26]>CN(C)C=O>[OH:26][CH2:25][CH2:27][NH:28][C:8]1[CH:9]=[CH:10][C:11]2[N:12]([C:14]([C:17]3[S:21][C:20]([C:22](=[O:24])[CH3:23])=[CH:19][CH:18]=3)=[CH:15][N:16]=2)[N:13]=1

Participants

Conditions

Temperature: 40 °C

Procedure

Cesium carbonate [534-17-8] (150 mg, 0.5 mmol) was added to a solution of 1-[5-(6-fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone (60 mg, 0.2 mmol) and ethanolamine [141-43-5] (29 mg, 0.5 mmol) in N,N-dimethylformamide (3 mL). The mixture was stirred at 40° C. for 1 h then partitioned between ethyl acetate and water. Analysis of the organic extract revealed preparation ratio of the desired arylamine product to the ether to be approximately 2:1. Preparative RP-HPLC isolated 22 mg of 1-{5-[6-(2-hydroxy-ethylamino)-imidazo[1,2-b]pyridazin-3-yl]-thiophen-2-yl}-ethanone as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.83 (s, 3H) 2.57 (s, 2H) 3.04 (t, J=5.68 Hz, 1H) 4.43 (t, J=5.68 Hz, 1H) 7.04 (d, J=9.60 Hz, 1H) 7.91 (d, J=4.04 Hz, 1H) 8.03 (d, J=4.04 Hz, 1H) 8.16 (d, J=9.60 Hz, 1H) 8.36 (s, 1H). LRMS (ESI) m/z 303.1 [(M+H)]+, calc'd for C14H14N4O2S: 302.36.

Workup

customthen partitioned between ethyl acetate and water
extractionAnalysis of the organic extract
custompreparation ratio of the desired arylamine product to the ether

Sources & evidence

ORD record: ord-84c305df3f97412688529f1b6ff4a299
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969565B2

Reaction notes

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