Water → HCID 86629542, compound

HRID 217201Notes

Reaction equation

HRID 217201 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][CH2:15][C:16]2[N:20]=[C:19]([C:21]3[O:29][C:28]4[CH:27]=[CH:26][N:25]=[C:24]([Cl:30])[C:23]=4[CH:22]=3)[O:18][N:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.O.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:30][C:24]1[C:23]2[CH:22]=[C:21]([C:19]3[O:18][N:17]=[C:16]([CH2:15][O:14][CH:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)[N:20]=3)[O:29][C:28]=2[CH:27]=[CH:26][N:25]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 57659465HCID 57659465, compound

Product 1

HCID 86629542HCID 86629542, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred solution of 4-[5-(4-chlorofuro[3,2-c]pyridin-2-yl)-[1,2,4]oxadiazol-3-ylmethoxy]piperidine-1-carboxylic acid tert-butyl ester (Example 57, 150 mg, 346 μmol) in CH2Cl2 (4 mL) was treated with H2O (6 μL) and TFA (1.5 mL). After 1 h, the reaction was concentrated in vacuo, then the excess TFA was removed through azeotropic distillation with PhMe under reduced pressure. The remainder was partitioned between EtOAc and 2M NaOH. The aqueous phase was extracted further with EtOAc, then the combined EtOAc extracts were washed with brine and dried (MgSO4). Filtration and solvent evaporation furnished 4-chloro-2-[3-(piperidin-4-yloxymethyl)-[1,2,4]oxadiazol-5-yl]furo[3,2-c]pyridine: m/z (ES+)=335.1 [M+H]+. A mixture of this amine (105 mg, 315 μmol), 2-bromopyrimidine (55 mg, 346 μmol) and DBU (95 μL, 630 μmol) in dioxane (2 mL) was stirred at ambient temperature for 16 h. The reaction was concentrated and the residue purified by column chromatography (EtOAc-IH, 3:7) to yield the title compound: RT=3.40 min; m/z (ES+)=413.1 [M+H]+.

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. customthe excess TFA was removed through azeotropic distillation with PhMe under reduced pressure
  3. customThe remainder was partitioned between EtOAc and 2M NaOH
  4. extractionThe aqueous phase was extracted further with EtOAc
  5. washthe combined EtOAc extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationFiltration and solvent evaporation

Sources & evidence

ORD record
ord-07a4c584646b47b48899ec0372dd575e
Source dataset
uspto-grants-2012_06
Patent number
US08193359B2

Reaction notes

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