Trifluoroacetic acid → 5-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]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide

HRID 1499526Notes

Reaction equation

HRID 1499526 reaction equation
C(OC([NH:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22]([NH:24][C:25]1[C:26]([N:35]2[CH2:40][C@H:39]([CH3:41])[C@@H:38]([OH:42])[C@H:37]([NH:43]C(=O)OC(C)(C)C)[CH2:36]2)=[C:27]2[CH2:33][CH2:32][CH:31]([OH:34])[C:28]2=[N:29][CH:30]=1)=[O:23])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22]([NH:24][C:25]1[C:26]([N:35]2[CH2:40][C@H:39]([CH3:41])[C@@H:38]([OH:42])[C@H:37]([NH2:43])[CH2:36]2)=[C:27]2[CH2:33][CH2:32][CH:31]([OH:34])[C:28]2=[N:29][CH:30]=1)=[O:23]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86726756tert-Butyl {(3R,4R,5S)-1-[3-({[5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]-4-hydroxy-5-methylpiperidin-3-yl}carbamate

Product 1

HCID 867267575-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]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl {(3R,4R,5S)-1-[3-({[5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-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-c03f4363fed947b9b1cdda1c3f1be2f8
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

Loading…