Acetic Acid → HCID 86755888, compound

HRID 365873Notes

Reaction equation

HRID 365873 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][NH:11]2)=[CH:4][C:3]=1[C:15]1[S:16][CH:17]=[CH:18][CH:19]=1.C=O.[C:22]([BH3-])#N.[Na+].C(O)(=O)C>CCO>[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[CH3:22])=[CH:4][C:3]=1[C:15]1[S:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 54306755HCID 54306755, compound

Product 1

HCID 86755888HCID 86755888, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 6-chloro-3-(2-(S)-pyrrolidinylmethoxy)-5-(2-thienyl)pyridine from step 152b above (48 mg, 0.14 mmol) in EtOH (2 mL) was added formalin (37%, 2 mL), sodium cyanoborohydride (50 mg, 0.72 mmol) and acetic acid (0.05 mL), and the mixture was stirred at 25° C. for 24 h. The solvent was concentrated, and solid NaHCO3 was added to the residue. At pH 8 the mixture was extracted with EtOAc, which was dried (MgSO4) and concentrated. (44 mg, 100%). The residue was converted to the salt by treatment with hydrogen chloride in Et2O/THF to afford the title compound: mp 160-163° C.; 1H NMR (D2O) δ1.86-1.96 (m, 2H), 2.06 (m, 1H), 2.24 (m, 1H), 2.88 (s, 3H), 3.09 (m, 1H), 3.61 (m, 1H), 3.72 (m, 1H), 4.12 (dd, 1H, J=3.5, 7.0 Hz), 4.27 (dd, 1H, J=1.5, 7.0 Hz), 7.05 (dd, 1H, J=2.0, 3.0 Hz), 7.34 (d, 1H, J=2.0 Hz), 7.41 (d, 1H, J=2.0 Hz), 7.47 (d, 1H, J=3.0 Hz), 7.83 (d, 1H, J=1.5 Hz); MS (CI/NH3) m/z 309 (M+H)+. Anal. Calcd for C15H17ClN2OS·HCl·0.3 H2O: C, 51.37; H, 5.35; N, 7.99. Found: C, 51.38; H, 5.47; N, 7.85

Workup

  1. concentrationThe solvent was concentrated
  2. additionsolid NaHCO3 was added to the residue
  3. extractionAt pH 8 the mixture was extracted with EtOAc, which
  4. dry with materialwas dried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-785b9faf6adb48ba82d5720b712a33f8
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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