Diisopropylethylamine → 8-Aza-bicyclo[3.2.1]octane-8-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

HRID 630918Notes

Reaction equation

HRID 630918 reaction equation
[CH:1]12[N:8]([C:9](Cl)=[O:10])[CH:5]([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH2:2]2.[F:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][NH2:20])=[N:17][CH:18]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][NH:20][C:9]([N:8]2[CH:5]3[CH2:6][CH2:7][CH:1]2[CH2:2][CH2:3][CH2:4]3)=[O:10])=[N:17][CH:18]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 122475358-Azabicyclo[3.2.1]octane-8-carbonyl chlorideHCID 199167865-Fluoro-2-hydrazinylpyridine

Product 1

HCID 866872038-Aza-bicyclo[3.2.1]octane-8-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazideYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Intermediate 122a (240 mg, 1.38 mmol) and (5-fluoro-pyridin-2-yl)-hydrazine (176 mg, 1.38 mmol) in DCM (10 mL) was added DIPEA (721 μL, 4.15 mmol) and the reaction stirred for 5 days. The reaction was then partitioned between DCM and water. The aqueous phase was extracted with DCM (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 0-10% MeOH in DCM to give the title compound (170 mg, 47%). LCMS (Method 3): Rt 2.31 min, m/z 265 [MH+].

Workup

  1. customThe reaction was then partitioned between DCM and water
  2. extractionThe aqueous phase was extracted with DCM (×3)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by FCC on silica

Sources & evidence

ORD record
ord-b2923eaa8bb24cebb76972f29d2f8769
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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