Formaldehyde → HCID 86755886, compound

HRID 365868Notes

Reaction equation

HRID 365868 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:15])=[CH:4][C:3]=1[C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1.C=O>C(O)=O>[ClH:1].[ClH:1].[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:15])=[CH:4][C:3]=1[C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 54218913HCID 54218913, compound

Product 1

HCID 86755886HCID 86755886, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
80 °C

Procedure

To 6-Chloro-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)-5-(3-pyridinyl)pyridine obtained from step a above (250 mg, 0.64 mmol) was added formalin (37%, 4 mL) and formic acid (2 mL), and the mixture was heated at 80° C. for 10 h. The solvent was concentrated, and solid NaHCO3 was added to the residue. At pH 8 the mixture was extracted with CH2Cl2, which was dried (MgSO4) and concentrated. The residue was chromatographed (silica gel; CH2Cl2/MeOH/NH4OH, 10:1:0.1) to afford the free base of the title compound (162 mg, 83% yield). The base was converted to the salt by treatment with HCl in Et2O to give the title compound (130 mg, 73%): mp 108-110° C.; 1H NMR (D2O) δ2.0-2.30 (m, 2H), 2.40 (m, 1H), 3.03 (s, 3H), 3.25 (m, 1H), 3.65-3.82 (m, 2H), 3.94 (m, 1H), 4.39 (dd, 1H, J=6.0, 11.0 Hz), 4.57 (dd, 1H, J=3.0, 11.0 Hz), 7.69 (d, 1H, J=3.0 Hz), 8.17 (m, 1H), 8.28 (d, 1H, J=3.0 Hz), 8.74 (d, 1H, J=8.0 Hz), 8.86 (d, 1H, J=5.5 Hz), 9.01 (s, 1H). MS (CI/NH3) m/z 304 (M+H)+, 607 (2M+H)+. Anal. Calcd for C16H18ClN3O·2.4 HCl·0.2 Et2O: C, 49.69; H, 5.56; N, 10.35. Found: C, 49.77; H, 5.38; N, 10.11. [α]25D -1.5 (c 0.2, MeOH).

Workup

  1. concentrationThe solvent was concentrated
  2. additionsolid NaHCO3 was added to the residue
  3. extractionAt pH 8 the mixture was extracted with CH2Cl2, which
  4. dry with materialwas dried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was chromatographed (silica gel; CH2Cl2/MeOH/NH4OH, 10:1:0.1)

Sources & evidence

ORD record
ord-e967dbc50eab4f80bf1ebd70ee56e448
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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