Dichloromethane methanol → HCID 22293784, compound

HRID 967362Notes

Reaction equation

HRID 967362 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH2:13][N:14]([C:17](=[O:19])[CH3:18])[CH2:15][CH2:16][C:11]=3[N:10]([CH2:20][CH:21]([OH:33])[CH2:22][N:23]3[CH2:32][CH2:31][C:26]4(OCC[O:27]4)[CH2:25][CH2:24]3)[N:9]=2)=[CH:4][CH:3]=1.CO.C(Cl)Cl>Cl.C(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>[C:17]([N:14]1[CH2:15][CH2:16][C:11]2[N:10]([CH2:20][CH:21]([OH:33])[CH2:22][N:23]3[CH2:32][CH2:31][C:26](=[O:27])[CH2:25][CH2:24]3)[N:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[C:12]=2[CH2:13]1)(=[O:19])[CH3:18]

Participants

6

Reactant 2

HCID 21226129Dichloromethane methanolHCID 22293841HCID 22293841, compound

Product 1

HCID 22293784HCID 22293784, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6212ChloroformSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of 0.50 g (0.96 mmol) of 1-{3-(4-chloro-phenyl)-1-[3-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-2-hydroxy-propyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-ethanone in 1 N HCl (2.0 mL) was heated to 65° C. for 48 h in a sealed vessel. The reaction was allowed to cool to room temperature and was diluted with CHCl3 (20 mL) and saturated NaHCO3 (20 mL). The aqueous phase was extracted with CHCl3 (2×10 mL) and the combined organic extracts were dried over Na2SO4 and the solvent was removed under reduced pressure. The crude material was then diluted with Ac2O (3.0 mL) and was stirred for 48 h. The solvent was removed under reduced pressure and the crude material was pumped down overnight. The resulting solid was dissolved in MeOH (5.0 mL) and a catalytic amount (0.05 g) of K2CO3 was added to the mixture and stirring was continued overnight. The reaction was then diluted with H2O (20 mL) and CH2Cl2 (20 mL) and the layers were separated. The aqueous phase was extracted with CH2Cl2 (2×10 mL) and the combined organic extracts were dried over Na2SO4 and the solvent was removed under reduced pressure. Purification by flash chromatography (silica, 0-10% MeOH/CH2Cl2) afforded 0.29 g (65% over 3 steps) of a white solid. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.35. MS (electrospray); m/z calculated for C22H27ClN4O3, [M+H]+, 431.18, observed 431.1. 1H NMR (400 MHz, CDCl3, a mixture of amide rotamers): 7.59 (d, J=8.3 Hz, 1H), 7.53 (d, J=8.6 Hz, 1H), 7.41 (d, J=8.5 Hz, 1H), 7.37 (d, J=8.5 Hz, 1H), 4.85 and 4.73 (A and B of AB quartet, Jab=15.8 Hz, 1H), 4.62 (s, 1H), 4.26-4.12 (m, 2H), 4.09-3.68 (m, 4H), 3.49 (s, 1.5H), 3.28 (s, 1.5H).

Workup

  1. temperatureto cool to room temperature
  2. extractionThe aqueous phase was extracted with CHCl3 (2×10 mL)
  3. dry with materialthe combined organic extracts were dried over Na2SO4
  4. customthe solvent was removed under reduced pressure
  5. additionThe crude material was then diluted with Ac2O (3.0 mL)
  6. customThe solvent was removed under reduced pressure
  7. waitthe crude material was pumped down overnight
  8. dissolutionThe resulting solid was dissolved in MeOH (5.0 mL)
  9. additiona catalytic amount (0.05 g) of K2CO3 was added to the mixture
  10. stirringstirring
  11. waitwas continued overnight
  12. additionThe reaction was then diluted with H2O (20 mL) and CH2Cl2 (20 mL)
  13. customthe layers were separated
  14. extractionThe aqueous phase was extracted with CH2Cl2 (2×10 mL)
  15. dry with materialthe combined organic extracts were dried over Na2SO4
  16. customthe solvent was removed under reduced pressure
  17. customPurification by flash chromatography (silica, 0-10% MeOH/CH2Cl2)
  18. customafforded 0.29 g (65% over 3 steps) of a white solid

Sources & evidence

ORD record
ord-b93f0272a62e454581b1a9c40f8cfd82
Source dataset
uspto-grants-2005_10
Patent number
US06953793B2

Reaction notes

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