(3S)-3-Amino-1-methyl-3-[3-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one → (5S)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]non-1-en-6-one

HRID 626882Notes

Reaction equation

[NH2:1][C@@:2]1([CH2:9][C:10]#[C:11][C:12]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)[CH:15]=[CH:14][N:13]=2)[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8]>CC#N.FC(F)(F)S([O-])(=O)=O.[Ag+]>[CH3:7][N:4]1[CH2:5][CH2:6][C@:2]2([N:1]=[C:11]([C:12]3[N:17]=[C:16]([C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=4)[CH:15]=[CH:14][N:13]=3)[CH2:10][CH2:9]2)[C:3]1=[O:8]

Participants

Conditions

Temperature: 20 °C

Procedure

Silver trifluoromethanesulphonate (23.34 mg, 0.0900 mmol) was added to a solution of (3S)-3-amino-1-methyl-3-[3-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one (which may be prepared as described in Description 8) (340 mg, 0.9100 mmol) in MeCN (10 mL) and the reaction was stirred at 20° C. for 18 hrs. Additional AgOTf (0.1 eq) was added and stirring was continued for 3 days. Additional AgOTf was added and stirring was continued for a further 3 days. The solvent was evaporated and the residue was dissolved in EtOAc/satd. NaHCO3. The phases were separated and the organic layer was dried (Na2SO4) and the solvent evaporated to afford (5S)-7-methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]non-1-en-6-one (D9) (340 mg, 0.9082 mmol, 100% yield) as an amber oil.

Workup

stirringstirring
waitwas continued for 3 days
stirringstirring
waitwas continued for a further 3 days
customThe solvent was evaporated
dissolutionthe residue was dissolved in EtOAc/satd
customThe phases were separated
dry with materialthe organic layer was dried (Na2SO4)
customthe solvent evaporated

Sources & evidence

ORD record: ord-13bbaa85e3cf4bd8b2595850ee65523f
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309254B2

Reaction notes

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