Ammonium Chloride → HCID 66582477, compound

HRID 1972515Notes

Reaction equation

HRID 1972515 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([OH:27])([CH3:26])[C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[C@@H:11]([CH2:28][C:29](=O)[CH3:30])[CH2:10]1)(=[O:8])=[O:7].[O:32]1[CH2:35][CH:34]([NH2:36])[CH2:33]1.[BH4-].[Na+].[NH4+].[Cl-]>C1COCC1.CO>[F:25][C:22]([F:23])([F:24])[C:21]([C:18]1[CH:17]=[CH:16][C:15]([N:12]2[CH2:13][CH2:14][N:9]([S:6]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)(=[O:7])=[O:8])[CH2:10][C@@H:11]2[CH2:28][CH:29]([NH:36][CH:34]2[CH2:35][O:32][CH2:33]2)[CH3:30])=[CH:20][CH:19]=1)([OH:27])[CH3:26]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 98339233-OxetanamineHCID 665826001-((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)-2-propanone

Product 1

HCID 66582477HCID 66582477, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)-2-propanone (100 mg, 0.210 mmol) and oxetan-3-amine (18.41 mg, 0.252 mmol, J & W PharmLab, Levittown, Pa.) in THF (10 mL) was cooled to 0° C. To this mixture was added Ti(O-iPr)4 (154 μL, 0.525 mmol, Sigma-Aldrich, St. Louis, Mo.). The mixture was stirred for 3 h and then a solution of sodium borohydride (11.91 mg, 0.315 mmol, Sigma-Aldrich, St. Louis, Mo.) in MeOH (1 mL) was added. The reaction mixture was stirred at ambient temperature for 4 h. Saturated aqueous NH4Cl was added and the mixture was filtered. The filtrate was concentrated and purified via reverse-phase preparative HPLC using a Phenomenex Gemini C18 column (150×30 mm, 10 μm) eluting with 0.1% TFA in MeCN/H2O (5% to 100% over 15 min) to give 1,1,1-trifluoro-2-(4-((2S)-2-(2-(3-oxetanylamino)propyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (28 mg) as a mixture of four isomers

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 4 h
  2. filtrationthe mixture was filtered
  3. concentrationThe filtrate was concentrated
  4. custompurified via reverse-phase preparative HPLC
  5. washeluting with 0.1% TFA in MeCN/H2O (5% to 100% over 15 min)

Sources & evidence

ORD record
ord-ae4ae4ea81e94553932b09286013140e
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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