Trifluoroacetic acid → 4-[5-({[(3R)-1-(2-cyanobenzyl)piperidin-3-yl]amino}carbonyl)-1H-indazol-3-yl]pyridinium trifluoroacetate
Reaction equation
[C:1]([C:3]1[CH:52]=[CH:51][CH:50]=[CH:49][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH2:9][C@@H:8]([NH:12][C:13]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:19]=[C:18]3[C:43]2[CH:48]=[CH:47][N:46]=[CH:45][CH:44]=2)=[O:14])[CH2:7]1)#[N:2].[C:53]([OH:59])([C:55]([F:58])([F:57])[F:56])=[O:54]>>[F:56][C:55]([F:58])([F:57])[C:53]([O-:59])=[O:54].[C:1]([C:3]1[CH:52]=[CH:51][CH:50]=[CH:49][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH2:9][C@@H:8]([NH:12][C:13]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[NH:20][N:19]=[C:18]3[C:43]2[CH:44]=[CH:45][NH+:46]=[CH:47][CH:48]=2)=[O:14])[CH2:7]1)#[N:2]Participants
Procedure
To a microwave vial equipped with a stir bar was added N-[(3R)-1-(2-cyanobenzyl)piperidin-3-yl]-3-pyridin-4-yl-1-trityl-1H-indazole-5-carboxamide (41.7 mg, 0.061 mmol) and TFA (1000 μl, 12.98 mmol). The reaction was stirred at room temperature for 20 minutes. After 20 minutes the LCMS indicates formation of the desired product. Triethylsilane (19.62 μl, 0.123 mmol) was addes, and the crude reaction was concentrated in vacuo. The crude was dissolved in 1 ml DMSO, filtered, and purified by reverse phase chromatography. The material was concentrated, and was then dissolved in acetonitrile and water. The compound was dried on the lyophilizer over 2 days to provide fluffy white solid. LCMS calc'd for C26H25N6O [M+H]+=437; found 437 1H NMR (600 MHz, CD3OD) δ 8.9 (d, 2H), 8.9 (s, 1H), 8.7 (d, 2H), 8.0 (d, 1H), 7.9 (d, 1H), 7.8 (s, 2H), 7.8 (d, 1H), 7.7 (m, 1H), 4.6 (s, 2H), 4.4 (m, 1H), 3.7 (m, 1H), 3.6 (m, 1H), 3.2 (m, 2H), 2.2 (m, 2H), 2.0 (m, 1H), 1.8 (m, 1H).
Workup
- customTo a microwave vial equipped with a stir bar
- waitAfter 20 minutes the LCMS indicates
Sources & evidence
- ORD record
- ord-759af97709a3425e8a0584b4cf8751d1
- Source dataset
- uspto-grants-2015_04
- Patent number
- US08999957B2
Reaction notes
Loading…