t-Butylammonium fluoride → 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 601538Notes

Reaction equation

HRID 601538 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[C:11](=[O:42])[N:12]([C:17]4[CH:22]=[CH:21][C:20]([N:23]5[CH2:28][CH2:27][CH:26]([O:29][Si](C(C)C)(C(C)C)C(C)C)[CH2:25][CH2:24]5)=[C:19]([O:40][CH3:41])[CH:18]=4)[CH2:13][CH2:14][C:15]=3[N:16]=2)=[CH:4][CH:3]=1.[F-].C([NH3+])(C)(C)C>C1COCC1.CCOC(C)=O>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:9][C:10]3[C:11](=[O:42])[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:40][CH3:41])[CH:18]=4)[CH2:13][CH2:14][C:15]=3[N:16]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 21866379t-Butylammonium fluorideHCID 575017382-(4-Chloro-phenyl)-5-[3-methoxy-4-(4-triisopropylsilanyloxy-piperidin-1-yl)-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 salt

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

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. washwash with 2N NH4Cl (20 mL)
  2. concentrationConcentrate the organic solution
  3. custompurify the crude material by flash chromatography
  4. customto give semi-pure material
  5. customTriturate the solids with ether

Sources & evidence

ORD record
ord-a385ccda641648cb850452255efd1089
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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