Hydrochloric Acid → 4-Amino-2-(methylsulfanyl)pyrimidine-5-carbaldehyde

HRID 270704

Reaction equation

[NH2:1][C:2]1[C:7]([C:8]#N)=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=1.[H-].C([Al+]CC(C)C)C(C)C.Cl.C([O-])([O-])=[O:24].[Na+].[Na+]>C1COCC1>[NH2:1][C:2]1[C:7]([CH:8]=[O:24])=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-amino-2-(methylthio)pyrimidine-5-carbonitrile (3.0 g, 18.05 mmol) in THF (100 mL) is added diisobutylaluminum hydride (41.52 mL, 1.0 M in CH2Cl2, 41.52 mmol) at 0° C. After the mixture is stirred for 2.5 hours at 0° C., hydrochloric acid (2N, 30 mL) is added and stirring is continued for 20 minutes. To the reaction mixture is added saturated Na2CO3 until a pH of 8 is achieved. The suspended material is filtered through Celit pad and washed with K2CO3 solution. The solution is diluted with EtOAc and washed with saturated K2CO3, brine and dried, filtered and concentrated to give crude product, which is purified by flash silica gel column, eluting with hexane (100%) gradient to hexane/ether (60/40%), to give the title intermediate as a solid (1.62 g, 53.1%).

Workup

stirringstirring
waitis continued for 20 minutes
filtrationThe suspended material is filtered through Celit pad
washwashed with K2CO3 solution
additionThe solution is diluted with EtOAc
washwashed with saturated K2CO3, brine
customdried
filtrationfiltered
concentrationconcentrated
customto give crude product, which
customis purified by flash silica gel column
washeluting with hexane (100%) gradient to hexane/ether (60/40%)

Sources & evidence

ORD record: ord-4f82a12b8b6b4e0b823e207cd72b0dda
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07449582B2

Linked notes

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