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

HRID 495098Notes

Reaction equation

HRID 495098 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].[CH3:16][S:17]([OH:20])(=[O:19])=[O:18].O.N>C1COCC1>[CH3:16][S:17]([OH:20])(=[O:19])=[O:18].[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

6

Reactant 4

HCID 222AmmoniaHCID 962WaterHCID 6395Methanesulfonic AcidHCID 10131048Sofinicline

Product 1

HCID 11559172(1S,5S)-3-(5,6-Dichloro-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane methanesulfonate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

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 methylsulfonic acid (Aldrich, freshly prepared 1M in THF, 0.6 mL, 0.6 mmol). The mixture was then stirred at ambient temperature for 6 h. White solid started to precipitate. The solid was then filtered and dried (110 mg, yield, 65%). M.p. 144-152° C. Solubility: >50 mg/mL (water). 1H NMR (CD3OD, 300 MHZ) δ 2.69 (s, 3H)), 3.07 (dd, J=10.5, 6.5 Hz, 1H), 3.18 (dd, J=12.2, 4.7 Hz, 1H), 3.44-3.52 (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), 5.04 (dd, J=7.2, 5.1 Hz, 1H), 7.54 (d, J=2.7 Hz, 1H), 7.96 (d, J=3.0 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(110 mg, yield, 65%)

Sources & evidence

ORD record
ord-d813c9e7d0dd4439800b34436af9c61d
Source dataset
uspto-grants-2009_05
Patent number
US07538226B2

Reaction notes

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