Formic Acid → 4-[({7-[(2,6-Difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylic Acid

HRID 1486343Notes

Reaction equation

[F:1][C:2]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:30])[C:14]([C:15]([NH:17][C:18]34[CH2:25][CH2:24][C:21]([C:26]([O:28]C)=[O:27])([CH2:22][CH2:23]3)[CH2:20][CH2:19]4)=[O:16])=[C:10]2[CH:9]=[C:8]([CH3:31])[CH:7]=1.[OH-].[Li+].C(O)=O>C1COCC1.CO>[F:36][C:32]1[CH:33]=[CH:34][CH:35]=[C:2]([F:1])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:30])[C:14]([C:15]([NH:17][C:18]34[CH2:19][CH2:20][C:21]([C:26]([OH:28])=[O:27])([CH2:22][CH2:23]3)[CH2:24][CH2:25]4)=[O:16])=[C:10]2[CH:9]=[C:8]([CH3:31])[CH:7]=1

Participants

Conditions

Temperature: 40 °C

Procedure

56 mg (0.113 mmol) of methyl 4-[({7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylate from Example 152 were dissolved in 1.1 ml of THF/methanol (5/1), and 8.1 mg (0.339 mmol) of lithium hydroxide were added. The mixture was stirred at 40° C. for 10 h. After cooling, the mixture was acidified with 20 μl of formic acid and purified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.05% formic acid). 41 mg of the target compound were obtained (75% of theory).

Workup

temperatureAfter cooling
custompurified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.05% formic acid)

Sources & evidence

ORD record: ord-46b23565130a46e49a81d737be5e11a1
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422285B2

Reaction notes

Loading…