1,4-Dioxane → HCID 178499447, compound

HRID 707314Notes

Reaction equation

HRID 707314 reaction equation
CC(C)([O-])C.[Na+].[S:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH:16][C@H:17]1[CH2:20][C@H:19]([NH2:21])[CH2:18]1.Cl[C:23]1[C:28]([CH2:29][C:30]([O:32][CH3:33])=[O:31])=[CH:27][CH:26]=[CH:25][N:24]=1.O1CCOCC1>O.[Pd](Cl)Cl>[S:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH:16][C@H:17]1[CH2:18][C@H:19]([NH:21][C:23]2[C:28]([CH2:29][C:30]([O:32][CH3:33])=[O:31])=[CH:27][CH:26]=[CH:25][N:24]=2)[CH2:20]1.[S:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH:16][C@H:17]1[CH2:18][C@H:19]([N:21]2[C:23]3=[N:24][CH:25]=[CH:26][CH:27]=[C:28]3[CH2:29][C:30]2=[O:31])[CH2:20]1

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 19771888(2-Chloro-pyridin-3-yl)-acetic acid methyl esterHCID 23676156Sodium t-butoxideHCID 178511738HCID 178511738, compound2×

Product 2

HCID 178499447HCID 178499447, compoundYield 18.19%HCID 178515350HCID 178515350, compoundYield 2.277%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolvent

Procedure

Sodium tert-butoxide (0.844 mL, 6.89 mmol), [dicyclohexyl(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine]2-(2-aminoethyl)phenyl)palladium(II) chloride (125 mg, 0.157 mmol), trans-N1-(benzo[d]thiazol-2-yl)cyclobutane-1,3-diamine (intermediate 11, 687 mg, 3.13 mmol), methyl 2-(2-chloropyridin-3-yl)acetate (640 mg, 3.45 mmol) and dry dioxane (5 mL) were sealed in a microwave vessel under argon. The mixture was stirred for 4 hours at room temperature. The reaction mixture was diluted with water (mL) and extracted with ethyl acetate. The organic extract was washed with water and dried over magnesium sulfate. Evaporation in vacuo gave the crude material as a tan solid. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g, hexane to ethyl acetate gradient), to provide methyl 2-(2-((trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)amino)pyridin-3-yl)acetate (210 mg, 0.570 mmol, 18.19% yield) and 1-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (24 mg, 0.071 mmol, 2.277% yield) as white solid. M+1: 337. 1H NMR (400 MHz, MeOH) δ ppm 2.44-2.53 (m, 2 H) 3.48-3.57 (m, 2 H) 3.62 (s, 2 H) 4.62-4.70 (m, 1 H) 5.30 (quin, J=8.66 Hz, 1 H) 7.03-7.13 (m, 2 H) 7.25-7.31 (m, 1 H) 7.48 (d, J=8.02 Hz, 1 H) 7.61-7.66 (m, 2 H) 8.22 (d, J=4.69 Hz, 1 H)

Workup

  1. extractionextracted with ethyl acetate
  2. extractionThe organic extract
  3. washwas washed with water
  4. dry with materialdried over magnesium sulfate
  5. customEvaporation in vacuo
  6. customgave the crude material as a tan solid
  7. customThe crude material was absorbed onto a plug of silica gel
  8. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g, hexane to ethyl acetate gradient)

Sources & evidence

ORD record
ord-e8ee17447d8442bf9416392ccfcbeb85
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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