Hydrochloric Acid → 2-(4-Chloro-phenyl)-5-[4-(4-hydroxy-piperidin-1-yl)-3-methoxy-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride salt

HRID 601539Notes

Reaction equation

HRID 601539 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[C:11](=[O:32])[N:12]([C:17]4[CH:22]=[CH:21][C:20]([N:23]5[CH2:28][CH2:27][CH:26]([OH:29])[CH2:25][CH2:24]5)=[C:19]([O:30][CH3:31])[CH:18]=4)[CH2:13][CH2:14][C:15]=3[N:16]=2)=[CH:4][CH:3]=1.Cl>CO>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:9][C:10]3[C:11](=[O:32])[N:12]([C:17]4[CH:22]=[CH:21][C:20]([N:23]5[CH2:28][CH2:27][CH:26]([OH:29])[CH2:25][CH2:24]5)=[C:19]([O:30][CH3:31])[CH:18]=4)[CH2:13][CH2:14][C:15]=3[N:16]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 575017732-(4-Chloro-phenyl)-5-[4-(4-hydroxy-piperidin-1-yl)-3-methoxy-phenyl]-6,7-dihydro-5h-thiazolo[5,4-c]pyridin-4-one

Product 1

HCID 1317287422-(4-Chloro-phenyl)-5-[4-(4-hydroxy-piperidin-1-yl)-3-methoxy-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride saltYield 143.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Dissolve 2-(4-chloro-phenyl)-5-[3-methoxy-4-(4-triisopropylsilanyloxy-piperidin-1-yl)-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (681 mg, 1.09 mmol) in THF (10 mL) then add tert-butylammonium fluoride (1.0 M solution in THF, 1.30 mL, 1.30 mmol). Stir the solution at room temperature for 2 h, then dilute with EtOAc (50 mL) and wash with 2N NH4Cl (20 mL). Concentrate the organic solution and purify the crude material by flash chromatography, using 8% MeOH (2N NH3)/CHCl3 as eluent, to give semi-pure material. Triturate the solids with ether to give the title compound as the free base (265 mg, 52%). Mix 2-(4-chloro-phenyl)-5-[4-(4-hydroxy-piperidin-1-yl)-3-methoxy-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (53 mg, 0.11 mmol) in MeOH (1 mL) and add 1N HCl (2.0 mL, 2.0 mmol). Stir the mixture at room temperature until all the solids dissolve and then cool to −20° C. overnight. Collect the precipitate by filtration, wash with ether, and dry under vacuum to give the title compound (40 mg, 70%). MS (ES+) 470.0 (M+1)+. 1H NMR (400 MHz, DMSO-d6): δ 11.69 (s, 1H), 8.06 (d, 2H, J=8.4 Hz), 7.70 (s, 1H), 7.63 (d, 2H, J=8.4 Hz), 7.34 (s, 1H), 7.14 (s, 1H), 4.65 (s, 4H), 4.16 (t, 2H, J=6.8 Hz), 3.95 (s, 3H), 3.64-3.32 (m, 2H), 3.29 (t, 2H, J=7.0 Hz), 2.11-1.76 (m, 4H),

Workup

  1. dissolutiondissolve
  2. temperaturecool to −20° C. overnight
  3. customCollect the precipitate
  4. filtrationby filtration
  5. washwash with ether
  6. customdry under vacuum

Sources & evidence

ORD record
ord-32c6aa3a2723411e92eff826eec9c012
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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