Methanol → 4-(3-Amino-6-(6-oxopiperidin-3-yl)pyrazin-2-yl)-2-fluorobenzoic acid

HRID 596133Notes

Reaction equation

[NH2:1][C:2]1[C:3]([C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21]C)=[O:20])=[C:17]([F:25])[CH:16]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][C:11](=[O:14])[NH:10][CH2:9]2)=[CH:6][N:7]=1.CO.[Li+].[OH-]>C(O)(C(F)(F)F)=O.C1COCC1.O>[NH2:1][C:2]1[C:3]([C:15]2[CH:24]=[CH:23][C:18]([C:19]([OH:21])=[O:20])=[C:17]([F:25])[CH:16]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][C:11](=[O:14])[NH:10][CH2:9]2)=[CH:6][N:7]=1

Participants

Conditions

Temperature: 150 °C

Procedure

Methyl 4-(3-amino-6-(6-oxopiperidin-3-yl)pyrazin-2-yl)-2-fluorobenzoate (144 mg, 0.310 mmol) was dissolved in TFA (Volume: 3 mL) and heated at 150° C. for 30 min in microwave The solvent was evaporated in vacuo and the residue was azeotroped with toluene thrice to afford the crude debenzylated lactam. This crude product was dissolved in THF (Volume: 3 mL, Ratio: 3) and MeOH (Volume: 1.500 mL, Ratio: 1.5) and to the mixture was added LiOH (0.037 g, 1.550 mmol) dissolved in Water (Volume: 1.500 mL, Ratio: 1.5). The mixture was agitated at room temperature for 30 min and concentrated in vacuo and the residue neutralized with 2 mL (4.0 N HCl) and the solvent evaporated. The residue was azeotroped once with THF and once with toluene to afford the crude acid which was taken to the next step (assuming quantitative yield) without any further purification. LCMS (m/z): (MH+), 331.2, 0.44 min.

Workup

customwas evaporated in vacuo
customthe residue was azeotroped with toluene thrice
customto afford the crude debenzylated lactam
concentrationconcentrated in vacuo
customthe solvent evaporated
customThe residue was azeotroped once with THF and once with toluene

Sources & evidence

ORD record: ord-a24a467babe24b54ace534084e1fb1f5
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

Loading…