Water → N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide

HRID 1499505Notes

Reaction equation

HRID 1499505 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][CH:35]=[CH:34][C:33]=4[F:39])[N:26]=3)=[O:24])=[CH:20][N:19]=[C:18]3[O:40][CH2:41][CH2:42][C:17]=23)[CH2:11][C@H:10]1[NH:43]C(=O)OC(C)(C)C)(C(C)(C)C)(C)C.[H+].[H+].F[Si-2](F)(F)(F)(F)F.O.[NH4+].[OH-]>CC#N>[NH2:43][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:33]([F:39])=[CH:34][CH:35]=[CH:36][C:37]=4[F:38])[N:26]=3)=[O:24])=[CH:20][N:19]=[C:18]3[O:40][CH2:41][CH2:42][C:17]=23)[CH2:11]1

Participants

5

Reactant 3

HCID 962Water2×HCID 14923Ammonium HydroxideHCID 86726735tert-Butyl {(3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-[5-({[6-(2,6-difluorophenyl)-5-fluoropyridin-2-yl]carbonyl}amino)-2,3-dihydrofuro[2,3-b]pyridin-4-yl]-5-methylpiperidin-3-yl}carbamate

Product 1

HCID 86726736N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamideYield 16.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of tert-butyl {(3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-[5-({[6-(2,6-difluorophenyl)-5-fluoropyridin-2-yl]carbonyl}amino)-2,3-dihydrofuro[2,3-b]pyridin-4-yl]-5-methylpiperidin-3-yl}carbamate (24.9 mg, 0.0349 mmol) in MeCN (2.0 mL) was added a 1.7 M dihydrogen hexafluorosilicate solution in water (200 μL, 0.340 mmol). The mixture was stirred at 50° C. for 2 h. After cooling to room temperature, the reaction mixture was neutralized with a 14.8 M NH4OH solution in water (200 μL, 2.96 mmol), and was purified using RP-HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.) to afford the title compound as a white solid (2.8 mg, 16%). LCMS calc. for C25H25F3N5O3 (M+H)+: m/z=500.2. found 500.1.

Workup

  1. temperatureAfter cooling to room temperature
  2. customwas purified
  3. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-60168edd9ab74ab39ef37487d26be536
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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