Methanesulfonic Acid → Prexasertib mesylate

HRID 1878317Notes

Reaction equation

[NH2:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[C:7]=1[C:14]1[NH:18][N:17]=[C:16]([NH:19][C:20]2[N:21]=[CH:22][C:23]([C:26]#[N:27])=[N:24][CH:25]=2)[CH:15]=1.[CH3:28][S:29]([OH:32])(=[O:31])=[O:30]>CO>[CH3:28][S:29]([OH:32])(=[O:31])=[O:30].[NH2:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[C:7]=1[C:14]1[NH:18][N:17]=[C:16]([NH:19][C:20]2[N:21]=[CH:22][C:23]([C:26]#[N:27])=[N:24][CH:25]=2)[CH:15]=1

Participants

Conditions

Temperature: -15 °C

Procedure

5-(5-(2-(3-aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-ylamino)pyrazine-2-carbonitrile (1.0 g, 2.74 mmol) is suspended in MeOH (100 mL). A 1 M solution of methanesulfonic acid in MeOH (2.74 mL, 2.74 mmol) is added to the mixture dropwise with stirring. The solid nearly completely dissolves and is sonicated and stirred for 15 min, filtered, and concentrated to 50 mL. The solution is cooled overnight at −15° C. and the solid that forms is collected by filtration. The solid is dried in a vacuum oven overnight to give 0.938 g (74%) of a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 1.97 (m, 2H), 2.28 (s, 3H), 2.95 (m, 2H), 3.79 (s, 3H), 4.09 (t, J=5.9 Hz, 2H), 6.753 (d, J=8.4 Hz, 1H), 6.766 (d, J=8.4 Hz, 1H), 6.85 (br s, 1H), 7.33 (t, J=8.4 Hz, 1H), 7.67 (br s, 3H), 8.49 (br s, 1H), 8.64 (s, 1H), 10.70 (s, 1H), 12.31 (s, 1H). LC-ES/MS m/z 366.2 [M+1]+.

Workup

dissolutionThe solid nearly completely dissolves
customis sonicated
stirringstirred for 15 min
filtrationfiltered
concentrationconcentrated to 50 mL
filtrationthe solid that forms is collected by filtration
customThe solid is dried in a vacuum oven overnight

Sources & evidence

ORD record: ord-a68c2b94d67540679e63341605548bdc
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08314108B2

Reaction notes

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