Hydrochloric Acid → HCID 86726803, compound

HRID 1499578Notes

Reaction equation

HRID 1499578 reaction equation
C([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH:31][C:32]([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[C:36]([C:41]4[C:46]([F:47])=[CH:45][CH:44]=[CH:43][C:42]=4[F:48])[N:35]=3)=[O:33])[C:13]([N:14]3[CH2:19][C@H:18]([CH3:20])[C:17]([OH:22])([CH3:21])[C@H:16]([NH:23]C(OC(C)(C)C)=O)[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=O)C.[OH-].[Na+].Cl.O1CCOCC1>CO.C1COCC1>[NH2:23][C@H:16]1[C:17]([OH:22])([CH3:21])[C@@H:18]([CH3:20])[CH2:19][N:14]([C:13]2[C:12]([NH:31][C:32]([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[C:36]([C:41]4[C:46]([F:47])=[CH:45][CH:44]=[CH:43][C:42]=4[F:48])[N:35]=3)=[O:33])=[CH:11][N:10]=[C:9]3[CH:5]([OH:4])[CH2:6][CH2:7][C:8]=23)[CH2:15]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 86726802HCID 86726802, compound

Product 1

HCID 86726803HCID 86726803, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-{(3R,5S)-3-[(tert-Butoxycarbonyl)amino]-4-hydroxy-4,5-dimethylpiperidin-1-yl}-3-({[6-(2,6-difluorophenyl)-5-fluoropyridin-2-yl]carbonyl}amino)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate (118 mg, 0.176 mmol) was dissolved in a mixture of MeOH (1 mL) and THF (1 mL) and 0.5 M solution of aq. NaOH (1 mL, 0.5 mmol) was added. The reaction was stirred for 1 h, and then concentrated to dry under reduced pressure. To the residue was added 4.0 M solution of hydrogen chloride in dioxane (3 mL, 10 mmol). The reaction mixture was stirred for 1 h, and then evaporated to dryness. The resulting residue was dissolved in MeCN and purified by RP-HPLC (water SunFire™ C18 column, 19 mm×100 mm, 5 μm particle size, eluting with a gradient of MeCN/water containing 0.1% TFA, at flow rate of 30 mL/min.) to give four different diastereoisomers of the bis(trifluoroacetate) of the title compound as white solids.

Workup

  1. additionwas added
  2. concentrationconcentrated
  3. customto dry under reduced pressure
  4. stirringThe reaction mixture was stirred for 1 h
  5. customevaporated to dryness
  6. dissolutionThe resulting residue was dissolved in MeCN
  7. custompurified by RP-HPLC (water SunFire™ C18 column, 19 mm×100 mm, 5 μm particle size
  8. washeluting with a gradient of MeCN/water containing 0.1% TFA, at flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-6fcbbdeff8b04ae5ad094646e59a4399
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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