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

HRID 495097Notes

Reaction equation

HRID 495097 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:28])(=[O:27])[CH2:17][C:18]([CH2:23][C:24]([OH:26])=[O:25])([C:20]([OH:22])=[O:21])[OH:19].O.N>C1COCC1.CO>[C:16]([OH:28])(=[O:27])[CH2:17][C:18]([CH2:23][C:24]([OH:26])=[O:25])([C:20]([OH:22])=[O:21])[OH:19].[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].[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 311Citric AcidHCID 962WaterHCID 10131048Sofinicline

Product 1

HCID 131726816(1S, 5S)-3-(5,6-Dichloro-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane hemicitrate

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 citric acid (115 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 (160 mg, yield, 94%). M.p. 165-172° C. Solubility: 15.7 mg/mL (water). 1H NMR (CD3OD, 300 MHZ) δ 2.70 (d, J=15.2 Hz 1H), 2.78 (d, J=15.2 Hz 1H), 3.07 (dd, J=10.5, 6.5 Hz, 1H), 3.16 (dd, J=12.2, 4.7 Hz, 1H), 3.44-3.54 (m, 1H), 3.69 (dd, J=10.5, 4.8 Hz, 1H), 3.89 (d, J=10.5 Hz, 1H), 4.11 (d, J=12.2 Hz, 1H), 4.24 (dd, J=10.9, 8.5 Hz, 1H), 5.03 (dd, J=7.2, 5.1 Hz, 1H), 7.52 (d, J=3.0 Hz, 1H), 7.95 (d, J=2.8 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(160 mg, yield, 94%)

Sources & evidence

ORD record
ord-f2b637ee9aae4fb2b859b2df0d848af6
Source dataset
uspto-grants-2009_05
Patent number
US07538226B2

Reaction notes

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