Trifluoroacetic acid → N-{4-[(3S)-3-Aminopiperidin-1-yl]-7-oxo-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide

HRID 1499529Notes

Reaction equation

HRID 1499529 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]([C:15]([NH:17][C:18]2[C:19]([N:28]3[CH2:33][CH2:32][CH2:31][C@H:30]([NH:34]C(=O)OC(C)(C)C)[CH2:29]3)=[C:20]3[CH2:26][CH2:25][C:24](=[O:27])[C:21]3=[N:22][CH:23]=2)=[O:16])[CH:12]=[CH:11][C:10]=1[F:42].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:34][C@H:30]1[CH2:31][CH2:32][CH2:33][N:28]([C:19]2[C:18]([NH:17][C:15]([C:13]3[CH:12]=[CH:11][C:10]([F:42])=[C:9]([C:3]4[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=4[F:8])[N:14]=3)=[O:16])=[CH:23][N:22]=[C:21]3[C:24](=[O:27])[CH2:25][CH2:26][C:20]=23)[CH2:29]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86726759tert-Butyl {(3S)-1-[3-({[6-(2,6-difluorophenyl)-5-fluoropyridin-2-yl]carbonyl}amino)-7-oxo-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]piperidin-3-yl}carbamate

Product 1

HCID 86726760N-{4-[(3S)-3-Aminopiperidin-1-yl]-7-oxo-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamideYield 45.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl {(3S)-1-[3-({[6-(2,6-difluorophenyl)-5-fluoropyridin-2-yl]carbonyl}amino)-7-oxo-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]piperidin-3-yl}carbamate (6.0 mg, 0.010 mmol) in DCM (0.05 mL) and TFA (0.052 mL, 0.68 mmol) was stirred at room temperature for 20 min. The solution was then concentrated under reduced pressure. The residue was diluted with MeOH, filtered and purified by preparative LC-MS (XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH) to give the title compound as a white powder (2.2 mg, 44%). LCMS calc. for C25H23F3N5O2 (M+H)+: m/z=482.2. Found: 482.3.

Workup

  1. concentrationThe solution was then concentrated under reduced pressure
  2. additionThe residue was diluted with MeOH
  3. filtrationfiltered
  4. custompurified by preparative LC-MS (XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min.
  5. washeluting with a gradient of MeCN and water with 0.1% NH4OH)

Sources & evidence

ORD record
ord-878eb960805a4dc4bd72bd8c0f38e582
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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