Trifluoroacetic acid → 5-(8-(Piperidin-4-ylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-one

HRID 1093963Notes

Reaction equation

HRID 1093963 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[N:16]4[N:17]=[CH:18][N:19]=[C:15]4[C:14]([NH:20][CH:21]4[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]4)=[N:13][CH:12]=3)=[CH:8][CH:9]=2)[CH2:4][NH:3]1.FC(F)(F)C(O)=O>ClCCl.O>[NH:24]1[CH2:23][CH2:22][CH:21]([NH:20][C:14]2[C:15]3[N:16]([N:17]=[CH:18][N:19]=3)[C:11]([C:7]3[CH:6]=[C:5]4[C:10](=[CH:9][CH:8]=3)[C:2](=[O:1])[NH:3][CH2:4]4)=[CH:12][N:13]=2)[CH2:26][CH2:25]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 25115608Tert-butyl 4-(5-(1-oxoisoindolin-5-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)piperidine-1-carboxylate

Product 1

HCID 251153805-(8-(Piperidin-4-ylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-oneYield 20.4%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6344DichloromethaneSolvent

Procedure

The product of Step 2 (64 mg, 0.14 mmol) is suspended in dichloromethane (0.5 mL), trifluoroacetic acid (0.25 mL) and H2O (3 drops). The reaction mixture is stirred and room temperature for 40 min. The mixture is purged with nitrogen and then basified to pH 9 with 2M NaOH (aq.). The aqueous layer is extracted with dichoromethane and ethyl acetate. The combined organics are dried (MgSO4) and solvent is removed in vacuo to yield the title compound as an off-white solid (10 mg, 20%). 1H-NMR (400 MHz, d6-DMSO) =1.13 (t, 2H, J=6.8), 1.57-1.70 (m, 2H), 2.58-2.72 (m, 2H), 3.02-3.08 (m, 2H), 4.13-4.30 (m, 1H), 4.50 (s, 2H), 7.81 (d, 1H, J=8), 7.92 (s, 1H), 8.03-8.11 (m, 2H), 8.18 (s, 1H), 8.63 (s, 1H), 8.69 (s, 1H). LCMS: Rt 6.55 min (86.9%), m/z (APCI) 350 (M+H)+.

Workup

  1. customThe mixture is purged with nitrogen
  2. extractionThe aqueous layer is extracted with dichoromethane and ethyl acetate
  3. dry with materialThe combined organics are dried (MgSO4) and solvent
  4. customis removed in vacuo

Sources & evidence

ORD record
ord-55c84ea7424c42e28b5acf5ae228e276
Source dataset
uspto-grants-2012_03
Patent number
US08133895B2

Reaction notes

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