Sodium Bicarbonate → 3-(6-Chloro-3-pyridinyl)-3,8-diazabicyclo[3.2.1]octane dihydrochloride

HRID 914744Notes

Reaction equation

HRID 914744 reaction equation
N[C:2]1[N:7]=[CH:6][C:5]([N:8]2[CH2:14][CH:13]3[N:15](C(OC(C)(C)C)=O)[CH:10]([CH2:11][CH2:12]3)[CH2:9]2)=[CH:4][CH:3]=1.N([O-])=O.[Na+].C([O-])(O)=O.[Na+].[ClH:32].CCOCC>Cl>[ClH:32].[ClH:32].[Cl:32][C:2]1[N:7]=[CH:6][C:5]([N:8]2[CH2:14][CH:13]3[NH:15][CH:10]([CH2:11][CH2:12]3)[CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 10953452Ether hydrochlorideHCID 23668193Sodium NitriteHCID 67357179Tert-butyl 3-(6-amino-3-pyridinyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 865904003-(6-Chloro-3-pyridinyl)-3,8-diazabicyclo[3.2.1]octane dihydrochlorideYield 43%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

The product from Example 11A (0.03 g; 0.103 mmol) in 12M HCl (0.13 mL) was treated with sodium nitrite (10 mg, 0.129 mmol) at 0° C. The reaction mixture was allowed to warm to ambient temperature and stir overnight. The mixture was neutralized by addition of NaHCO3 and then extracted with CH2Cl2. The extracts were dried (Na2SO4), concentrated under reduced pressure, and the residue purified on SiO2 (10% MeOH/CH2Cl2/1% NH4OH) to provide the free base. The free base was treated with 1M HCl/ether to provide the title compound (43% yield). 1H NMR free base (CDCl3, 300 MHz) δ 1.8 (m, 4H), 2.1 (br s, 1H, exchangeable), 3.0 (d.K=11 Hz, 2H), 3.4-3.7 (br s, 2H), 7.0-7.2 (m, 2H0, 7.9 (m, 1H).

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialThe extracts were dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customthe residue purified on SiO2 (10% MeOH/CH2Cl2/1% NH4OH)
  5. customto provide the free base

Sources & evidence

ORD record
ord-d94de876e96e4f539e6f9e7341cfc200
Source dataset
uspto-grants-2007_09
Patent number
US07265115B2

Reaction notes

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