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

HRID 495100Notes

Reaction equation

HRID 495100 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 444972Fumaric AcidHCID 10131048Sofinicline

Product 1

HCID 11639080(1S,5S)-3-(5,6-Dichloro-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane fumarate

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 fumaric 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 (150 mg, yield, 84%). M.p. 198-202° C. Solubility: 2.9 mg/mL (water). 1H NMR (CD3OD, 300 MHZ) δ 3.07 (dd, J=10.5, 6.5 Hz, 1H), 3.17 (dd, J=12.2, 4.7 Hz, 1H), 3.44-3.55 (m, 1H), 3.71 (dd, J=10.5, 4.8 Hz, 1H), 3.90 (d, J=10.5 Hz, 1H), 4.11 (d, J=12.2 Hz, 1H), 4.26 (dd, J=10.9, 8.5 Hz, 1H), 5.04 (dd, J=7.2, 5.1 Hz, 1H), 6.68 (s, 2H), 7.53 (d, J=3.1 Hz, 1H), 7.96 (d, J=2.7 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(150 mg, yield, 84%)

Sources & evidence

ORD record
ord-8a0c693a00d54b5ebb3db6fb59ab271c
Source dataset
uspto-grants-2009_05
Patent number
US07538226B2

Reaction notes

Loading…