Sodium Hydroxide → 2-(4-Chloro-phenyl)-5-{4-[1-(2-hydroxy-ethyl)-azetidin-3-yloxy]-3-methoxy-phenyl}-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride salt

HRID 554875Notes

Reaction equation

HRID 554875 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.[OH:31][CH:32]1[CH2:37]OC(O)CO1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl>[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]([CH2:37][CH2:32][OH:31])[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

6

Reactant 4

HCID 14798Sodium HydroxideHCID 186078Glycolaldehyde dimerHCID 5049666Sodium triacetoxyborohydrideHCID 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 1317292572-(4-Chloro-phenyl)-5-{4-[1-(2-hydroxy-ethyl)-azetidin-3-yloxy]-3-methoxy-phenyl}-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride saltYield 22%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Dissolve 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (500 mg, 1.13 mmol) and 2,5-dihydroxy-1,4-dioxane (68 mg, 1.13 mmol) in dry 1,2-dichloroethane (6.66 mL). Add sodium triacetoxyborohydride (500 mg, 2.26 mmol) and stir overnight at room temperature. Add 1 N NaOH solution to the reaction mixture and extract with CH2Cl2 (2×25 mL). Combine the organic portions and wash with water (2×25 mL). Dry the organic layer with Na2SO4, filter, and concentrate in vacuo. Purify on HPLC, 4.6×75 mm XBridge® C18, Eluent: Reverse phase gradient 5-95% MeOH/water 0.1% TFA in 10 min, 2 mL/min. Re-dissolve the acquired material in CHCl3 and add 1 N HCl/Et2O solution (160 μL), followed by concentration in vacuo to give 65 mg (13%) of the title compound. ES/MS m/z (35Cl) 486.0 [M+1]+.

Workup

  1. extractionextract with CH2Cl2 (2×25 mL)
  2. washCombine the organic portions and wash with water (2×25 mL)
  3. dry with materialDry the organic layer with Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify on HPLC, 4.6×75 mm XBridge® C18, Eluent
  7. additionadd 1 N HCl/Et2O solution (160 μL)
  8. concentrationfollowed by concentration in vacuo

Sources & evidence

ORD record
ord-fbd79d2badab4e838c9af93ee743e467
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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