Hydrazine hydrate (1:1) → Linagliptin

HRID 530956Notes

Reaction equation

[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH2:12][N:13]2[C:22](=[O:23])[C:21]3[N:20]([CH2:24][C:25]#[C:26][CH3:27])[C:19]([N:28]4[CH2:33][CH2:32][CH2:31][C@@H:30]([N:34]5C(=O)C6=CC(C)=CC=C6C5=O)[CH2:29]4)=[N:18][C:17]=3[N:16]([CH3:46])[C:14]2=[O:15])[N:3]=1.O.NN>C(O)C>[CH3:27][C:26]#[C:25][CH2:24][N:20]1[C:19]([N:28]2[CH2:29][C@H:30]([NH2:34])[CH2:31][CH2:32][CH2:33]2)=[N:18][C:17]2[N:16]([CH3:46])[C:14]([N:13]([CH2:12][C:4]3[N:3]=[C:2]([CH3:1])[C:11]4[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=4[N:5]=3)[C:22](=[O:23])[C:21]1=2)=[O:15]

Participants

Conditions

Temperature: 79 °C

Procedure

In a clean round bottom flask, 9 ml of ethanol, 90 mg of 1-[(4-Methylquinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-(3-(R)-4-methylphthalimidopiperidin-1-yl)-xanthine & 0.9 ml of hydrazine hydrate were charged. The temperature of the reaction mass was raised to 78-80° C. & the reaction mass was maintained for 3 hours. The reaction mass was cooled to 50° C. & ethanol was distilled off. 9 ml methylene dichloride was added to the obtained residue & stirred at RT to get the solid. Undesired solid was filtered. The filtrate was concentrated & 9 ml methyl tert butyl ether was added to the residue to get the solid Linagliptin. Reaction mass was stirred at RT & filtered. Wet cake was washed with 2 ml IPA. Dry wt 45 mg

Workup

temperaturethe reaction mass was maintained for 3 hours
temperatureThe reaction mass was cooled to 50° C.
distillationethanol was distilled off
addition9 ml methylene dichloride was added to the obtained residue
customto get the solid
filtrationUndesired solid was filtered
concentrationThe filtrate was concentrated
addition9 ml methyl tert butyl ether was added to the residue

Sources & evidence

ORD record: ord-34b03fe401514054bde76bb756edfacb
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09353114B2

Reaction notes

Loading…