Dimethylformamide dimethyl acetal → N-(2-{[5-(2,6-Dichlorophenyl)-6-oxo-6H-pyrimido[1,6-b]pyridazin-2-yl]sulfanyl}benzyl)-3-fluoro-5-(morpholin-4-yl)benzamide

HRID 2096251Notes

Reaction equation

[NH2:1][C:2](=[O:42])[CH:3]([C:12]1[N:17]=[N:16][C:15]([S:18][C:19]2[CH:41]=[CH:40][CH:39]=[CH:38][C:20]=2[CH2:21][NH:22][C:23](=[O:37])[C:24]2[CH:29]=[C:28]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH:27]=[C:26]([F:36])[CH:25]=2)=[CH:14][CH:13]=1)[C:4]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:5]=1[Cl:11].[CH3:43]N(C(OC)OC)C>C1(C)C=CC=CC=1>[Cl:10][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]([Cl:11])[C:4]=1[C:3]1[C:2](=[O:42])[N:1]=[CH:43][N:17]2[C:12]=1[CH:13]=[CH:14][C:15]([S:18][C:19]1[CH:41]=[CH:40][CH:39]=[CH:38][C:20]=1[CH2:21][NH:22][C:23](=[O:37])[C:24]1[CH:29]=[C:28]([N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)[CH:27]=[C:26]([F:36])[CH:25]=1)=[N:16]2

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of N-[2-({6-[2-amino-1-(2,6-dichlorophenyl)-2-oxoethyl]pyridazin-3-yl}sulfanyl)benzyl]-3-fluoro-5-(morpholin-4-yl)benzamide (91 mg, 0.145 mmol) in toluene (4 mL) under an argon atmosphere was treated with DMF-DMA (0.042 mL, 0.315 mmol). The mixture was heated at 100° C. for 1.75 h, then cooled to RT and the precipitate separated by filtration to afford the title compound (77 mg, 84%) as a yellow powder. LCMS (Method 3): Rt 9.8 min, m/z 636 [MH+]. 1H NMR (400 MHz, DMSO-d6): 9.01 (1H, t, J 5.7), 8.82 (1H, d, J 0.7), 7.70 (1H, dd, J 7.7, 1.2), 7.60 (2H, m), 7.58-7.52 (2H, m), 7.49 (1H, dd, J 8.9, 7.3), 7.42 (1H, td, J 7.3, 2), 7.23 (1H, br t, J 1.6), 7.04-6.98 (2H, m), 6.93-6.86 (2H, m), 4.66 (2H, d, J 5.6), 3.73 (4H, t, J 4.7), 3.17 (4H, t, J 4.7).

Workup

temperaturecooled to RT
customthe precipitate separated by filtration

Sources & evidence

ORD record: ord-5c9777b4b5a146cca873db994fa98ed8
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08450314B2

Reaction notes

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