Acetic Acid → 1-Methyl-6-[3-(trifluoromethyl)benzyl]-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid
Reaction equation
[F:1][C:2]([F:50])([F:49])[C:3]1[CH:4]=[C:5]([CH:46]=[CH:47][CH:48]=1)[CH2:6][N:7]1[C:15]2[C:10](=[N:11][C:12]([N:16](C(OC(C)(C)C)=O)[NH:17][C:18](OC(C)(C)C)=O)=[CH:13][CH:14]=2)[CH:9]=C1C(OCC1C=CC=C(C(F)(F)F)C=1)=O.[OH-].[Na+].[CH3:53]O.[C:55]([OH:58])(=[O:57])[CH3:56]>>[CH3:53][C:18]1[N:11]2[C:10]3[CH:9]=[C:56]([C:55]([OH:58])=[O:57])[N:7]([CH2:6][C:5]4[CH:46]=[CH:47][CH:48]=[C:3]([C:2]([F:50])([F:49])[F:1])[CH:4]=4)[C:15]=3[CH:14]=[CH:13][C:12]2=[N:16][N:17]=1Participants
5
Reactant 4
Product 1
Procedure
Di-tert-butyl 1-[1-[3-(trifluoromethyl)benzyl]-2-({[3-(trifluoromethyl)benzyl]oxy}carbonyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]hydrazine-1,2-dicarboxylate (0.28 g, 0.40 mmol, from Step 2) in acetic acid (10 mL) was heated to 180° C. in the microwave for 5 minutes. The acetic acid was then removed in vacuo. The residue was dissolved in THF (10 mL) and 1.0 M NaOH (10 mL, 10 mmol) was added. After stirring for 20 minutes, MeOH was added to make the mixture monophasic and the product was purified by preparative HPLC-MS (Waters XBridge C18, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH). Yield: 45 mg, 30%.
Workup
- customThe acetic acid was then removed in vacuo
- dissolutionThe residue was dissolved in THF (10 mL)
- customthe product was purified by preparative HPLC-MS (Waters XBridge C18
- washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)
Sources & evidence
- ORD record
- ord-40b010163cf844abba7841c944f4bf84
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09309246B2
Reaction notes
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