Acetic Acid → 5-((5-(2-Methoxy-6-((4-methoxybenzyl)oxy)phenyl)-1H-pyrazol-3-yl)amino)pyrazine-2-carbonitrile

HRID 1878320Notes

Reaction equation

C(O)C.C(O)(=O)C.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:11]=1[C:26](=O)/[CH:27]=[C:28](\[NH:31][C:32]1[N:33]=[CH:34][C:35]([C:38]#[N:39])=[N:36][CH:37]=1)/SC.O.[NH2:42][NH2:43]>C(O)C.C(O)(=O)C>[CH3:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:11]=1[C:26]1[NH:43][N:42]=[C:28]([NH:31][C:32]2[N:33]=[CH:34][C:35]([C:38]#[N:39])=[N:36][CH:37]=2)[CH:27]=1

Participants

Conditions

Temperature: 67.5 °C

Procedure

In a 20 L container are combined ethanol (11.28 L) and acetic acid (318 mL, 5.545 mol). The reaction is vented to a bleach scrubber with a nitrogen purge. (E)-5-(3-(2-Methoxy-6-(4-methoxybenzyloxy)phenyl)-1-(methylthio)-3-oxoprop-1-enylamino)pyrazine-2-carbonitrile (940 g, 1.931 mol) and the ethanol/acetic acid solution are added to a 22 L reaction flask. To the resulting brown slurry is added hydrazine monohydrate (197 g, 3.935 mol), resulting in a slight exotherm. The resulting yellow slurry is slowly heated to 65-70° C. and monitored by HPLC. The duration of the reaction is less than one hour. The thick slurry is slowly cooled over 1-2 h to less than 30° C. The slurry is filtered and washed with cold ethanol. The material is vacuum dried at 40° C. affording (820 g, 99.1%) of the title compound. mp 215-117° C.; ES/MS m/z 429.2 [M+1]+.

Workup

custompurge
customresulting in a slight exotherm
waitThe duration of the reaction is less than one hour
temperatureThe thick slurry is slowly cooled over 1-2 h to less than 30° C
filtrationThe slurry is filtered
washwashed with cold ethanol
customdried at 40° C.

Sources & evidence

ORD record: ord-ee1cf999875c43b7b8d2678573ce2843
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08314108B2

Reaction notes

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