Hydrochloric Acid → 5,6-Dichloro-2-(1-methyl-2-(R)-pyrrolidinyl)furo[3,2-b]pyridine hydrochloride

HRID 611587Notes

Reaction equation

HRID 611587 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C@H:11]3[CH2:15][CH2:14][CH2:13][NH:12]3)[O:10][C:5]2=[CH:4][C:3]=1[Cl:16].Cl.[CH2:18]=O>C(O)=O.CCOCC>[ClH:1].[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C@H:11]3[CH2:15][CH2:14][CH2:13][N:12]3[CH3:18])[O:10][C:5]2=[CH:4][C:3]=1[Cl:16]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 538109675,6-Dichloro-2-(2-(R)-pyrrolidinyl)furo[3,2-b]pyridine

Product 1

HCID 882109045,6-Dichloro-2-(1-methyl-2-(R)-pyrrolidinyl)furo[3,2-b]pyridine hydrochlorideYield 46%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
60 °C

Procedure

5,6-Dichloro-2-(2-(R)-pyrrolidinyl)furo[3,2-b]pyridine from Example 39b (56 mg, 0.22 mmol) was dissolved in an aqueous solution of 37% formaldehyde (excess) and 88% formic acid (excess). The aqueous mixture was heated to 60° C. for 1 hour and then allowed to cool to ambient temperature. The reaction mixture was washed with Et2O, basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The organic phases were combined, dried (MgSO4), concentrated and chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a solid. The solid was dissolved in Et2O (10 mL) and a saturated solution of HCl in Et2O was added dropwise. The solvent was removed and the product recrystallized from MeOH/Et2O to afford a white solid (31 mg, 46%): mp 244-246° C.; 1H NMR (D2O, 300 MHz) δ 2.27-2.37 (m, 2H), 2.47-2.71 (m, 2H), 2.93 (s, 3H), 3.38 (m, 1H), 3.78 (m, 1H), 4.81 (m, partially buried under H2O peak, 1H), 7.27 (s, 1H), 8.26 (s, 1H); MS (CI/NH3) m/z: 271 (M+H)+ ; Anal. Calcd for C12H12Cl2N2O.HCl: C, 46.85; H, 4.26; N, 9.11. Found: C, 46.53; H, 4.21; N, 8.82.

Workup

  1. temperatureto cool to ambient temperature
  2. washThe reaction mixture was washed with Et2O
  3. extractionextracted with CH2Cl2 (2×)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customchromatographed (silica gel; CHCl3 /MeOH, 98:2)
  7. customto afford a solid
  8. customThe solvent was removed
  9. customthe product recrystallized from MeOH/Et2O

Sources & evidence

ORD record
ord-3fef9e9629ff4b05907c8533379c3ab1
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

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