Triethylamine → 4-[1-(3,6-Dichloro-5-hydroxymethyl-pyrazin-2-yl)-piperidin-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

HRID 2066872Notes

Reaction equation

HRID 2066872 reaction equation
[Cl:1][C:2]1[C:3]([C:29](O)=[O:30])=[N:4][C:5]([Cl:28])=[C:6]([N:8]2[CH2:13][CH2:12][C:11](=[N:14][O:15][CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][CH:25]([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[CH2:10][CH2:9]2)[N:7]=1.C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+]>C1COCC1.O>[CH:25]([O:24][C:22]([N:19]1[CH2:18][CH2:17][CH:16]([O:15][N:14]=[C:11]2[CH2:12][CH2:13][N:8]([C:6]3[C:5]([Cl:28])=[N:4][C:3]([CH2:29][OH:30])=[C:2]([Cl:1])[N:7]=3)[CH2:9][CH2:10]2)[CH2:21][CH2:20]1)=[O:23])([CH3:27])[CH3:26]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 866550143,6-Dichloro-5-[4-(1-isopropoxycarbonyl-piperidin-4-yloxyimino)-piperidin-1-yl]-pyrazine-2-carboxylic acid

Product 1

HCID 583336024-[1-(3,6-Dichloro-5-hydroxymethyl-pyrazin-2-yl)-piperidin-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

The crude 56c obtained in the previous step was combined with triethylamine (50 μL, 0.36 mmol) in 2 mL of THF and treated at 0° C. with ethyl chloroformate (30 μL, 0.31 mmol). The mixture was stirred at room temperature for 4 h then it was added to a stirred suspension of sodium borohydride (32 mg, 0.84 mmol) in water and the stirring was continued for 3 h. The mixture was quenched with aqueous NaHCO3 (5 mL) and water (5 mL) and extracted with EtOAc (3×5 mL). The combined extracts were dried and concentrated and the residue was purified by reparative TLC(eluent: EtOAc) to afford 56-1: LC-MS 442.0 (MH+-18), tR=7.43 (Method 2). EC50: 35 nM.

Workup

  1. waitthe stirring was continued for 3 h
  2. customThe mixture was quenched with aqueous NaHCO3 (5 mL) and water (5 mL)
  3. extractionextracted with EtOAc (3×5 mL)
  4. customThe combined extracts were dried
  5. concentrationconcentrated
  6. customthe residue was purified by reparative TLC(eluent
  7. customEtOAc) to afford 56-1

Sources & evidence

ORD record
ord-a9b799327d294574a990bb5d258aa7c3
Source dataset
uspto-grants-2012_10
Patent number
US08293729B2

Reaction notes

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