Hydrochloric Acid → HCID 69215403, compound

HRID 272859Notes

Reaction equation

HRID 272859 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3([C:23]#[N:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[ClH:25]>O=[Pt]=O.C(O)(C)C>[ClH:25].[ClH:25].[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3([CH2:23][NH2:24])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[CH:15][CH:16]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 59837510HCID 59837510, compound

Product 1

HCID 69215403HCID 69215403, compound

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 4-[4-(3-piperidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-carbonitrile (1.45 g, 4.4 mmol), isopropanol (12 mL), concentrated HCl (350 μL), and PtO2 (115 mg) was stirred and hydrogenated to 50° C. overnight at atmospheric pressure. The mixture was filtrated over diatomaceous earth and concentrated. The residue was dissolved in DCM/MeOH mixture and washed with NaOH (1M). The organic layers were dried over Na2SO4, filtered and concentrated, purified by flash chromatography (10 g silica gel, DCM/MeOH (10% NH3)) to provide the title compound as free base (0.650 g, 44.5%). This was then converted to the dihydrochloride salt. 1H NMR (400 MHz, DMSO-D6) δ 10.66 (bs, 1H), 7.74 (bs, 3H), 7.32 (d, 2H), 6.97 (d, 2H), 4.07 (t, 2H), 3.73-3.65 (m, 2H), 3.47-3.28 (m, 4H), 3.18-3.10 (m, 2H), 2.98-2.81 (m, 4H), 2.25-2.16 (m, 2H), 2.14-2.06 (m, 2H), 1.90-1.67 (m, 7H), 1.44-1.31 (m, 1H).

Workup

  1. filtrationThe mixture was filtrated over diatomaceous earth
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in DCM/MeOH mixture
  4. washwashed with NaOH (1M)
  5. dry with materialThe organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash chromatography (10 g silica gel, DCM/MeOH (10% NH3))

Sources & evidence

ORD record
ord-0cf3678e60b440f6bdc92fd61f2687b3
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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