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

HRID 1499524Notes

Reaction equation

HRID 1499524 reaction equation
C(OC([NH:8][C:9]1[C:10]([C:24]([NH:26][C:27]2[C:28]([N:37]3[CH2:42][C@H:41]([CH3:43])[C@@H:40]([OH:44])[C@H:39]([NH:45]C(=O)OC(C)(C)C)[CH2:38]3)=[C:29]3[CH2:35][CH2:34][CH:33]([OH:36])[C:30]3=[N:31][CH:32]=2)=[O:25])=[N:11][C:12]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=2[F:23])=[C:13]([F:15])[CH:14]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C:9]1[C:10]([C:24]([NH:26][C:27]2[C:28]([N:37]3[CH2:42][C@H:41]([CH3:43])[C@@H:40]([OH:44])[C@H:39]([NH2:45])[CH2:38]3)=[C:29]3[CH2:35][CH2:34][CH:33]([OH:36])[C:30]3=[N:31][CH:32]=2)=[O:25])=[N:11][C:12]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=2[F:23])=[C:13]([F:15])[CH:14]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86726754tert-Butyl {(3R,4R,5S)-1-[3-({[3-[(tert-butoxycarbonyl)amino]-6-(2,6-difluorophenyl)-5-fluoropyridin-2-yl]carbonyl}amino)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]-4-hydroxy-5-methylpiperidin-3-yl}carbamate

Product 1

HCID 867267553-Amino-N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl {(3R,4R,5S)-1-[3-({[3-[(tert-butoxycarbonyl)amino]-6-(2,6-difluorophenyl)-5-fluoropyridin-2-yl]carbonyl}amino)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]-4-hydroxy-5-methylpiperidin-3-yl}carbamate (7.0 mg, 0.01 mmol) and 4.0 M TFA in DCM (2.0 mL) was stirred at room temperature for 1 h. After removal of the solvent 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 both diastereoisomers of the title compound as white powders. On analytical HPLC (Waters SunFire™ C18, 2.1×50 mm, 5 μm; flow rate 3 mL/min.; injection volume 2 μL; gradient from 2 to 80% B in 3 minutes (A=water with 0.025% TFA, B=MeCN)), the diastereoisomers had the following properties:

Workup

  1. customAfter removal of the solvent 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-b698391c72f8490285da6496f0a7374c
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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