Hydrochloric Acid → HCID 71233246, compound

HRID 2409937Notes

Reaction equation

HRID 2409937 reaction equation
[F:1][C:2]([F:39])([F:38])[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23]3[O:24][C:25]([C:28]4[CH:29]=[C:30]([CH:35]=[CH:36][CH:37]=4)[C:31]([O:33]C)=[O:32])=[CH:26][N:27]=3)[CH2:10]2)=[CH:5][CH:4]=1.[Li+].[OH-].Cl>CO.C1COCC1>[F:39][C:2]([F:1])([F:38])[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23]3[O:24][C:25]([C:28]4[CH:29]=[C:30]([CH:35]=[CH:36][CH:37]=4)[C:31]([OH:33])=[O:32])=[CH:26][N:27]=3)[CH2:10]2)=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 71233428HCID 71233428, compound

Product 1

HCID 71233246HCID 71233246, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 3-(2-(((1R,2R)-2-(((S)-1-(4-(trifluoromethyl)phenyl)piperidin-3-yl)amino)cyclohexyl)amino)oxazol-5-yl)benzoate (470 mg, 0.866 mmol) was dissolved in a mixed solvent of MeOH (3.5 mL) and THF (3.5 mL), then 2 M of aqueous LiOH (7 mL, 14 mmol) was added. The resultant mixture was stirred at rt for 16 h. LC/MS check showed the reaction was completed. The reaction was cooled in an ice-bath, 3 M HCl was added dropwise to adjust pH ˜3. The reaction mixture was concentrated. The resulting residue was purified using prep HPLC (Phenomenex Luna Axia, 5μ, 30×100 mm, 40-80% B, gradient over 10 min, hold at 80% B for 2 min). The desired fractions were concentraed to almost dryness, and the residue was lyophilized in CH3CN—H2O to afford the title compound (2 TFA salt) as a beign colored powder (465 mg, 0.615 mmol, 71.0% yield). Anal. Calcd. for C28H31F3N4O3 m/z 528.2, found: 529.1.

Workup

  1. temperatureThe reaction was cooled in an ice-bath
  2. concentrationThe reaction mixture was concentrated
  3. customThe resulting residue was purified
  4. customprep HPLC (Phenomenex Luna Axia, 5μ, 30×100 mm, 40-80% B, gradient over 10 min, hold at 80% B for 2 min)

Sources & evidence

ORD record
ord-4f2b132db587418391ba1f1046fd8c2d
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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