Ammonia → (1S,5S)-3-(5,6-Dichloro-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane maleate

HRID 899344Notes

Reaction equation

HRID 899344 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:15][C@@H:14]3[C@@H:11]([CH2:12][NH:13]3)[CH2:10]2)[CH:5]=[N:6][C:7]=1[Cl:8].[C:16]([OH:23])(=[O:22])/[CH:17]=[CH:18]\[C:19]([OH:21])=[O:20].O.N>C1COCC1.CO>[C:16]([OH:23])(=[O:22])/[CH:17]=[CH:18]\[C:19]([OH:21])=[O:20].[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:15][C@@H:14]3[C@@H:11]([CH2:12][NH:13]3)[CH2:10]2)[CH:5]=[N:6][C:7]=1[Cl:8]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 962WaterHCID 444266Maleic AcidHCID 10131048Sofinicline

Product 1

HCID 11631853(1S,5S)-3-(5,6-Dichloro-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane maleate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under N2, to a solution of the product of Example 5J (122 mg, 0.5 mmol) in THF (5 mL) was slowly added the solution of maleic acid (70 mg, 0.6 mmol) in MeOH (0.6 mL). The mixture was then stirred at ambient temperature for 6 h. White solid started to precipitate. The solid was then filtered and dried (140 mg, yield, 78%). M.p. 160–163° C. Solubility: 7.5 mg/mL (water). 1H NMR (CD3OD, 300 MHZ) δ 3.07 (dd, J=10.5, 6.5 Hz, 1H), 3.18 (dd, J=12.2, 4.7 Hz, 1H), 3.44–3.56 (m, 1H), 3.73 (dd, J=10.5, 4.8 Hz, 1H), 3.91 (d, J=10.5 Hz, 1H), 4.11 (d, J=12.2 Hz, 1H), 4.26 (dd, J=10.9, 8.5 Hz, 1H), 5.05 (dd, J=7.2, 5.1 Hz, 1H), 6.27 (s, 2H), 7.53 (d, J=2.7 Hz, 1H), 7.96 (d, J=2.9 Hz, 1H) ppm. MS (DCI/NH3) m/z 244 (M+H)+, 246 (M+H)+.

Workup

  1. customto precipitate
  2. filtrationThe solid was then filtered
  3. customdried
  4. custom(140 mg, yield, 78%)

Sources & evidence

ORD record
ord-27b313274ad0481ba23fe1880707eb4f
Source dataset
uspto-grants-2008_04
Patent number
US07354937B2

Reaction notes

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