Hydrochloric Acid → 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-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridine-2-carboxamide

HRID 1499597Notes

Reaction equation

HRID 1499597 reaction equation
[Si]([O:8][C@@H:9]1[C@@H:14]([CH3:15])[CH2:13][N:12]([C:16]2[C:21]([NH:22][C:23]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[C:27]([C:32]4[C:37]([F:38])=[CH:36][C:35]([CH2:39][O:40][CH3:41])=[CH:34][C:33]=4[F:42])[N:26]=3)=[O:24])=[CH:20][N:19]=[C:18]3[CH:43]([OH:46])[CH2:44][CH2:45][C:17]=23)[CH2:11][C@H:10]1[NH:47]C(=O)OC(C)(C)C)(C(C)(C)C)(C)C.Cl.O1CCOCC1>>[NH2:47][C@H:10]1[C@H:9]([OH:8])[C@@H:14]([CH3:15])[CH2:13][N:12]([C:16]2[C:21]([NH:22][C:23]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[C:27]([C:32]4[C:37]([F:38])=[CH:36][C:35]([CH2:39][O:40][CH3:41])=[CH:34][C:33]=4[F:42])[N:26]=3)=[O:24])=[CH:20][N:19]=[C:18]3[CH:43]([OH:46])[CH2:44][CH2:45][C:17]=23)[CH2:11]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86726812tert-butyl ((3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-{3-[({6-[2,6-difluoro-4-(methoxymethyl)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 86726813N-{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-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridine-2-carboxamide

Procedure

The alcohol intermediate prepared as described above was treated with 4.0 M HCl in dioxane (10 mL, 40 mmol) at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The 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 afford two diastereoisomers of the title compound as white powders.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe 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-43572e1b3b004e2ba887f401d1072e0b
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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