Acetic Acid → (1S,5S)-3-(5,6-Dichloro-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane acetate

HRID 899341Notes

Reaction equation

HRID 899341 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:19])(=[O:18])[CH3:17].O.N>C1COCC1>[C:16]([OH:19])(=[O:18])[CH3:17].[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 176Acetic AcidHCID 222AmmoniaHCID 962WaterHCID 10131048Sofinicline

Product 1

HCID 11601908(1S,5S)-3-(5,6-Dichloro-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane acetate

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 (anhydrous, 5 mL) was slowly added the solution of acetic acid (36 uL, 0.6 mmol) in THF (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 (110 mg, yield, 72%). M.p. 160–164° C. Solubility: 13.4 mg/mL (water). 1H NMR (CD3OD, 300 MHZ) δ 1.91 (s, 3H), 3.08 (dd, J=10.5, 6.4 Hz, 1H), 3.13 (dd, J=12.2, 4.8 Hz, 1H), 3.43–3.52 (m, 1H), 3.58 (dd, J=10.5, 4.8 Hz, 1H), 3.87 (d, J=10.5 Hz, 1H), 4.01 (d, J=11.8 Hz, 1H), 4.14 (dd, J=10.5, 8.5 Hz, 1H), 4.91 (dd, J=7.1, 4.7 Hz, 1H), 7.49 (d, J=2.7 Hz, 1H), 7.93 (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(110 mg, yield, 72%)

Sources & evidence

ORD record
ord-fdcc6af9b32542229cac22f0e1e5c0ec
Source dataset
uspto-grants-2008_04
Patent number
US07354937B2

Reaction notes

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