Carbonate Ion → Methyl 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(3R)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate

HRID 600537Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of methyl 3-hydroxy-5-[(3R)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate (Intermediate 12) (265 mg, 1 mmol), azetidin-1-yl-(5-chloropyrazin-2-yl)methanone (Intermediate 32) (298 mg, 1.5 mmol) and polymer supported-carbonate (860 mg, 2.5 mmol) in DMA (5 mL) was stirred at 100° C. for 2 hours. The mixture was filtered and the DMA was removed under reduced pressure. The residue was purified by flash chromatography on silica eluting with 20-100% ethyl acetate in isohexane then 10% methanol in DCM to afford the product (292 mg, 68%). 1H NMR δ (300 MHz, CDCl3) 2.13-2.27 (m, 1H), 2.31-2.44 (m, 2H), 2.53-2.66 (m, 1H), 2.94 (s, 3H), 3.35-3.58 (m, 2H), 3.90 (s, 3H), 4.26 (t, 2H), 4.68 (t, 2H), 4.93 (t, 1H), 7.14 (s, 1H), 7.46 (s, 1H), 7.60 (s, 1H), 8.31 (s, 1H), 8.84 (s, 1H); m/z 427 (M+H)+

Workup

filtrationThe mixture was filtered
customthe DMA was removed under reduced pressure
customThe residue was purified by flash chromatography on silica eluting with 20-100% ethyl acetate in isohexane

Sources & evidence

ORD record: ord-970bed0cad424bbf80167ae44b84f917
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07902200B2

Reaction notes

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