2-Amino-2-methyl-1-propanol → (E)-N'-(2-cyano-4-(3-(1-hydroxy-2-methylpropan-2-yl)thioureido)phenyl)-N,N-dimethylformimidamide

HRID 240538Notes

Reaction equation

[C:1](N1C=CN=C1)(N1C=CN=C1)=[S:2].[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]=[CH:21][N:22]([CH3:24])[CH3:23])=[C:16]([C:25]#[N:26])[CH:15]=1.[NH2:27][C:28]([CH3:32])([CH3:31])[CH2:29][OH:30]>C1COCC1>[C:25]([C:16]1[CH:15]=[C:14]([NH:13][C:1]([NH:27][C:28]([CH3:32])([CH3:31])[CH2:29][OH:30])=[S:2])[CH:19]=[CH:18][C:17]=1[N:20]=[CH:21][N:22]([CH3:23])[CH3:24])#[N:26]

Participants

Conditions

Temperature: -10 °C

Procedure

To a cooled (−10° C.) solution of thiocarbonyldiimidazole (211 g, 1.178 mol) in THF (1.5 L) was added slowly via cannula a solution of N′-(4-amino-2-cyanophenyl)-N,N-dimethylformamidine (201.6 g, 1.071 mol) in THF (1.5 L). After stirring at −10° C. for 25 minutes, a solution of 2-amino-2-methylpropan-1-ol (120 g, 1.4 mol) in THF (500 mL) was slowly added to the mixture. After warming to room temperature and stirring for 16 hours, the mixture was washed with saturated sodium chloride (2×2 L). The combined aqueous layers were extracted with MTBE (2 L) and ethyl acetate (4×1 L). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The residue was crystallized with MTBE and ethyl acetate to provide the product (116.9 g, 34%) as yellow solid.

Workup

temperatureAfter warming to room temperature
stirringstirring for 16 hours
washthe mixture was washed with saturated sodium chloride (2×2 L)
extractionThe combined aqueous layers were extracted with MTBE (2 L) and ethyl acetate (4×1 L)
dry with materialThe combined organic layers were dried over MgSO4
concentrationconcentrated under reduced pressure
customThe residue was crystallized with MTBE and ethyl acetate

Sources & evidence

ORD record: ord-b96d1819f765449ab8c04f1a0cab566d
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08648087B2

Reaction notes

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