Acetic Acid → HCID 9822805, compound

HRID 365871Notes

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[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1.C=O.[C:24]([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[CH3:24])=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of 6-Chloro-5-(4-chlorophenyl)-3-(2-(S)-pyrrolidinylmethoxy)pyridine from step 150b above (270 mg, 0.75 mmol) in EtOH (5.0 mL) was added formalin (37%, 5 mL), sodium cyanoborohydride (240 mg, 3.75 mmol) and acetic acid (0.15 mL), and the mixture was stirred at 25° C. for 16 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. (320 mg). The residue was converted to the salt by treatment with hydrogen chloride in Et2O/THF to afford the title compound (270 mg, 96%): mp 183-185° C.; 1H NMR (CD3OD) δ2.00-2.32 (m, 3H), 2.41 (m, 1H), 3.08 (s, 3H), 3.15 (m, 1H), 3.75 (m, 1H), 3.92 (m, 1H), 4.37 (dd, 1H, J=7.0, 11.0 Hz), 4.53 (dd, 1H, J=3, 11.0 Hz), 7.43-7.53 (m, 4H), 7.56 (d, 1H, J=4.5 Hz), 8.20 (d, 1H, J=3.0 Hz); MS (CI/NH3) m/z 337 (M+H)+. Anal. Calcd for C17H18Cl2N2O·1.3 HCl·0.1 H2O: C, 52.84; H, 5.09; N, 7.25. Found: C, 52.84; H, 4.84; N, 7.58. [α]25D -6.6 (c 0.42, MeOH).

Workup

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

Sources & evidence

ORD record: ord-13754029d7f54555aabab30bf9104100
Source dataset: uspto-grants-2000_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06127386

Reaction notes

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