Acetic Acid → 2-(4-Chloro-phenyl)-5-[4-(1-cyclopropyl-azetidin-3-yloxy)-3-methoxy-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride salt

HRID 554876Notes

Reaction equation

HRID 554876 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH2:17][CH2:16][C:15]4[N:18]=[C:19]([C:21]5[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=5)[S:20][C:14]=4[C:13]3=[O:28])=[CH:8][C:7]=2[O:29][CH3:30])[CH2:2]1.C(O[C:34]1(O[Si](C)(C)C)[CH2:36][CH2:35]1)C.C(O)(=O)C.C([BH3-])#N.[Na+].[OH-].[Na+]>CO>[ClH:27].[Cl:27][C:24]1[CH:23]=[CH:22][C:21]([C:19]2[S:20][C:14]3[C:13](=[O:28])[N:12]([C:9]4[CH:10]=[CH:11][C:6]([O:5][CH:3]5[CH2:4][N:1]([CH:34]6[CH2:36][CH2:35]6)[CH2:2]5)=[C:7]([O:29][CH3:30])[CH:8]=4)[CH2:17][CH2:16][C:15]=3[N:18]=2)=[CH:26][CH:25]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 249911625-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one

Product 1

HCID 1317292582-(4-Chloro-phenyl)-5-[4-(1-cyclopropyl-azetidin-3-yloxy)-3-methoxy-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride saltYield 64%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Mix molecular sieves (60 mg, type 3A), 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (1.00 g, 2.26 mmoles), [(1-ethoxycyclopropyl)oxy]trimethylsilane (685.2 μL, 3.39 mmoles), and acetic acid (648 μL, 11.31 mmoles) in dry methanol (11.4 mL). Reflux the mixture for 3 h. Cool the mixture to room temperature, add sodium cyanoborohydride (300 mg, 4.53 mmol) and slowly warm to 40° C. for 1 h. Cool the mixture and add 1 N NaOH solution. Extract the aqueous layer with CHCl3 (3×25 mL). Purify on HPLC, 4.6×150 mm Kromasil® silica, Eluent: 40% THF/heptane 0.1% N,N′-dimethylethylamine, 1 mL/min. Re-dissolve the material in CHCl3 and add 1 N HCl/Et2O solution (750 μL). Concentrate the solvent in vacuo to give 375 mg (34%) of the title compound. ES/MS m/z (35Cl) 482.2 [M+1]+.

Workup

  1. temperatureReflux the mixture for 3 h
  2. temperatureslowly warm to 40° C. for 1 h
  3. temperatureCool the mixture
  4. extractionExtract the aqueous layer with CHCl3 (3×25 mL)
  5. customPurify on HPLC, 4.6×150 mm Kromasil® silica, Eluent
  6. additionadd 1 N HCl/Et2O solution (750 μL)
  7. concentrationConcentrate the solvent in vacuo

Sources & evidence

ORD record
ord-ff3586cee4a64fa389f9efa9bcbb4354
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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