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

HRID 495099
Notes
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Reaction equation

HRID 495099 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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 887Methanol
Solvent
HCID 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-6649c5f3404a47bfb64ffefcb5d56e86
Source dataset
uspto-grants-2009_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07538226B2

Reaction notes

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