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

HRID 1499503Notes

Reaction equation

HRID 1499503 reaction equation
C(OC([NH:8][C@H:9]1[C@H:14]([O:15][Si](C(C)(C)C)(C)C)[C@@H:13]([CH3:23])[CH2:12][N:11]([C:24]2[C:29]([NH:30][C:31]([C:33]3[N:34]=[C:35]([C:46]4[C:51]([F:52])=[CH:50][CH:49]=[CH:48][C:47]=4[F:53])[S:36][C:37]=3[NH:38]C(=O)OC(C)(C)C)=[O:32])=[CH:28][N:27]=[C:26]3[O:54][CH2:55][CH2:56][C:25]=23)[CH2:10]1)=O)(C)(C)C.[H+].[H+].F[Si-2](F)(F)(F)(F)F.O.[NH4+].[OH-]>CC#N>[NH2:38][C:37]1[S:36][C:35]([C:46]2[C:47]([F:53])=[CH:48][CH:49]=[CH:50][C:51]=2[F:52])=[N:34][C:33]=1[C:31]([NH:30][C:29]1[C:24]([N:11]2[CH2:12][C@H:13]([CH3:23])[C@@H:14]([OH:15])[C@H:9]([NH2:8])[CH2:10]2)=[C:25]2[CH2:56][CH2:55][O:54][C:26]2=[N:27][CH:28]=1)=[O:32]

Participants

5

Reactant 3

HCID 962Water2×HCID 14923Ammonium HydroxideHCID 86726733tert-Butyl [4-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)-2,3-dihydrofuro[2,3-b]pyridin-5-yl]amino}carbonyl)-2-(2,6-difluorophenyl)-1,3-thiazol-5-yl]carbamate

Product 1

HCID 867267345-Amino-N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamideYield 33.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of tert-butyl [4-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)-2,3-dihydrofuro[2,3-b]pyridin-5-yl]amino}carbonyl)-2-(2,6-difluorophenyl)-1,3-thiazol-5-yl]carbamate (29.2 mg, 0.0357 mmol) in MeCN (2.0 mL) was added a 1.7 M dihydrogen hexafluorosilicate solution in water (0.5 mL, 0.8 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 (300 μL, 4.44 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 (6.0 mg, 33%). LCMS calc. for C23H25F2N6O3S (M+H)+: m/z=503.2. found 503.2.

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-5bb68ffc046f4c9d9ad199cea3261a67
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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