Ethanolamine → Linagliptin

HRID 530959Notes

Reaction equation

HRID 530959 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.C(CN)O>C1(C)C=CC=CC=1>[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

4

Reactant 2

HCID 700EthanolamineHCID 1317356521-[(4-Methylquinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-(3(R)-4-methylphthalimidopiperidine-yl)-xanthine

Product 1

HCID 10096344Linagliptin

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
92.5 °C

Procedure

In a clean round bottom flask, 10 gm of 1-[(4-Methylquinazolin-2yl)methyl]-3-methyl-7-(2-butin-1yl)-8-(3(R)-4-methylphthalimidopiperidine-yl) xanthine and 100 ml of toluene were charged. 10 ml of ethanolamine was added to the reaction mass and heated to 90-95° C. to complete the reaction. The reaction mass was cooled to 80° C. and the layers were separated. The organic phase was distilled under vacuum to get crude linagliptin. Dry wt: 7.50 gm HPLC purity: 97.95% Impurity X: 0.69%

Workup

  1. customthe reaction
  2. temperatureThe reaction mass was cooled to 80° C.
  3. customthe layers were separated
  4. distillationThe organic phase was distilled under vacuum

Sources & evidence

ORD record
ord-030705a5f397494385eaf95f75ecedd1
Source dataset
uspto-grants-2016_05
Patent number
US09353114B2

Reaction notes

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