Hydrochloric Acid → N-[4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl]-6-[2,6-difluoro-4-(oxan-3-yloxy)phenyl]-5-fluoropyridine-2-carboxamide

HRID 1499618Notes

Reaction equation

HRID 1499618 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][O:11][CH2:10]2)[CH:5]=[C:4]([F:15])[C:3]=1[C:16]1[N:21]=[C:20]([C:22]([NH:24][C:25]2[C:26]([N:35]3[CH2:40][C@H:39]([CH3:41])[CH2:38][C@H:37]([NH:42]C(=O)OC(C)(C)C)[CH2:36]3)=[C:27]3[CH2:33][CH2:32][CH:31]([OH:34])[C:28]3=[N:29][CH:30]=2)=[O:23])[CH:19]=[CH:18][C:17]=1[F:50].Cl.O1CCOCC1>>[NH2:42][C@H:37]1[CH2:38][C@@H:39]([CH3:41])[CH2:40][N:35]([C:26]2[C:25]([NH:24][C:22]([C:20]3[CH:19]=[CH:18][C:17]([F:50])=[C:16]([C:3]4[C:2]([F:1])=[CH:7][C:6]([O:8][CH:9]5[CH2:14][CH2:13][CH2:12][O:11][CH2:10]5)=[CH:5][C:4]=4[F:15])[N:21]=3)=[O:23])=[CH:30][N:29]=[C:28]3[CH:31]([OH:34])[CH2:32][CH2:33][C:27]=23)[CH2:36]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86726835tert-butyl ((3S,5R)-1-{3-[({6-[2,6-difluoro-4-(tetrahydro-2H-pyran-3-yloxy)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl}-5-methylpiperidin-3-yl)carbamate

Product 1

HCID 86726836N-[4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl]-6-[2,6-difluoro-4-(oxan-3-yloxy)phenyl]-5-fluoropyridine-2-carboxamide

Procedure

The alcohol intermediate made above was treated with 4.0 M HCl in dioxane (1 mL, 5 mmol) at room temperature overnight. The solution was concentrated under reduced pressure and the resulting residue was purified by preparative LCMS (Waters SunFire™ C18 column, 19 mm×100 mm, 5 μm particle size, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.) to give two separated diastereoisomers of the title compound as white powders.

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. customthe resulting residue was purified by preparative LCMS (Waters SunFire™ C18 column, 19 mm×100 mm, 5 μm particle size
  3. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-ff5feaa540ba402b96d56f400f66a9b6
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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