Trifluoroacetic acid → HCID 86726698, compound

HRID 1499454Notes

Reaction equation

HRID 1499454 reaction equation
C(O)(C(F)(F)F)=O.C(OC([NH:15][C:16]1[S:20][C:19]([C:21]2[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=2[F:28])=[N:18][C:17]=1[C:29]([NH:31][C:32]1[C:33]([N:43]2[CH2:48][CH2:47][CH2:46][C@H:45]([NH:49]C(=O)OC(C)(C)C)[CH2:44]2)=[C:34]2[CH2:40][CH2:39][CH:38]([C:41]#[N:42])[C:35]2=[N:36][CH:37]=1)=[O:30])=O)(C)(C)C>C(Cl)Cl>[NH2:15][C:16]1[S:20][C:19]([C:21]2[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=2[F:28])=[N:18][C:17]=1[C:29]([NH:31][C:32]1[C:33]([N:43]2[CH2:48][CH2:47][CH2:46][C@H:45]([NH2:49])[CH2:44]2)=[C:34]2[CH2:40][CH2:39][CH:38]([C:41]#[N:42])[C:35]2=[N:36][CH:37]=1)=[O:30]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86726699HCID 86726699, compound

Product 1

HCID 86726698HCID 86726698, compoundYield 112.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.02 mL, 0.3 mmol) was added to a solution of tert-butyl {(3S)-1-[3-({[5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-7-cyano-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]piperidin-3-yl}carbamate (5.0 mg, 0.0072 mmol) in DCM (0.009 mL). The reaction mixture was stirred at room temperature for 15 min., then evaporated under reduced pressure. The resulting mixture was diluted with MeOH and neutralized with small amount of NH4OH. After filtration, the crude product was purified by preparative LC-MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min., eluting with a gradient of MeCN and water with 0.15% NH4OH) to give the title compound (4 mg) as a mixture of two diastereoisomers, which was further purified by chiral preparative LC (Phenomenex Lux® Cellulose-1 column, 21.2×250 mm, 5 μm particle, flow rate 18 mL/min., isocratic eluting with 45% EtOH in hexanes) to give the title compound as two separated diastereoisomers.

Workup

  1. customevaporated under reduced pressure
  2. additionThe resulting mixture was diluted with MeOH and neutralized with small amount of NH4OH
  3. filtrationAfter filtration
  4. customthe crude product was purified by preparative LC-MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min.
  5. washeluting with a gradient of MeCN and water with 0.15% NH4OH)

Sources & evidence

ORD record
ord-4d2c668e03ca47b3bbffe2d8f9004f6e
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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