Potassium Phosphate, Tribasic → HCID 117843510, compound

HRID 2209187Notes

Reaction equation

HRID 2209187 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]([O:17][C@@H:18]([C@@H:20]2[CH2:24][C:23](=[O:25])[NH:22][CH2:21]2)[CH3:19])[C:10]2[S:14][C:13]([CH3:15])=[N:12][C:11]=2[CH:16]=1)(=O)=O.[CH3:28][O:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][C:35]=1[O:36][CH3:37].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.[Cl-].[Na+].O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:28][O:29][C:30]1[CH:31]=[C:32]([C:7]2[CH:8]=[C:9]([O:17][C@@H:18]([C@H:20]3[CH2:21][NH:22][C:23](=[O:25])[CH2:24]3)[CH3:19])[C:10]3[S:14][C:13]([CH3:15])=[N:12][C:11]=3[CH:16]=2)[CH:33]=[CH:34][C:35]=1[O:36][CH3:37]

Participants

9

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27347023,4-Dimethoxyphenylboronic acidHCID 117843368HCID 117843368, compound

Product 1

HCID 117843510HCID 117843510, compound

Reagents, catalysts & solvents 5

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

2-methyl-7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl trifluoromethanesulfonate (4.06) (32 mg, 0.075 mmol), 3,4-dimethoxyphenylboronic acid (27 mg, 0.15 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.5 mg, 0.002 mmol), and potassium phosphate (53 mg, 0.25 mmol) were taken up in 1,4-dioxane (1 mL) and water (0.11 mL). The stirred mixture was heated to 100 deg. C. After 4 h, the reaction mixture was diluted with EtOAc (2 mL), water (1 mL), and brine (1 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (4×1.5 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated to afford a crude residue that was purified by silica gel chromatography (0-15% MeOH in DCM) to provide (R)-4-((R)-1-(5-(3,4-dimethoxyphenyl)-2-methylbenzo[d]thiazol-7-yloxy)ethyl)pyrrolidin-2-one (4.29). LCMS-ESI+ (m/z): [M+H]+ calcd for C22H25N2O4S: 413.2; found: 413.1. 1H NMR (400 MHz, Chloroform-d) δ 7.76 (d, J=1.3 Hz, 1H), 7.18-7.12 (m, 2H), 6.98-6.94 (m, 2H), 6.02 (s, 1H), 4.68-4.59 (m, 1H), 3.95 (s, 3H), 3.93 (s, 3H), 3.58-3.50 (m, 1H), 3.35 (dd, J=9.6, 6.6 Hz, 1H), 2.94-2.84 (m, 1H), 2.83 (s, 3H), 2.59-2.43 (m, 2H), 1.41 (d, J=6.1 Hz, 3H).

Workup

  1. temperatureThe stirred mixture was heated to 100 deg. C
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with EtOAc (4×1.5 mL)
  4. dry with materialThe combined organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a crude residue that
  8. customwas purified by silica gel chromatography (0-15% MeOH in DCM)

Sources & evidence

ORD record
ord-5726859d9a5d411d9aa1fbade8a49425
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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