Tetrahydrofuran → HCID 86709319, compound

HRID 529406Notes

Reaction equation

HRID 529406 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1[CH:8]=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1[C:5]2([NH:20][S:21]([C:23]([CH3:26])([CH3:25])[CH3:24])=[O:22])[CH2:17][CH2:18][OH:19].C1COCC1.Br[CH2:33][C:34]#[N:35].[OH-].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1[CH:8]=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1[C:5]2([NH:20][S:21]([C:23]([CH3:26])([CH3:25])[CH3:24])=[O:22])[CH2:17][CH2:18][O:19][CH2:33][C:34]#[N:35]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11534Bromoacetonitrile2×HCID 14798Sodium HydroxideHCID 86709317HCID 86709317, compound

Product 1

HCID 86709319HCID 86709319, compound

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolvent

Procedure

A 100 mL RBF was charged with N-(7-bromo-3-chloro-5-(2-hydroxyethyl)-5H-chromeno[2,3-c]pyridin-5-yl)-2-methylpropane-2-sulfinamide (625 mg, 1.359 mmol), tetrabutylammonium hydrogen sulfate (138 mg, 0.408 mmol), THF (6.80 mL), and bromoacetonitrile (0.852 mL, 12.23 mmol) to give a cloudy, light brown solution. The resulting solution was stirred vigorously for 5 min. Then a 2N aq. solution of sodium hydroxide (13.600 mL, 27.2 mmol) was added in one portion. The solution changed into dark brown color. 3 Hrs later, LCMS showed an incomplete conversion (SM: product=1:1.5). 1 additional molar equivalent of BrCH2CN was added, and the mixture was stirred for 1 hr. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with saturated NaCl aqueous solution, dried over MgSO4, filtered and concentrated to give the crude material as a brown 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), eluting with a gradient of 25 to 40 to 80% DCM/MeOH/NH4OH (90:10:1) in 40% EtOAc in heptane to yield N-(7-bromo-3-chloro-5-(2-(cyanomethoxy)ethyl)-5H-chromeno[2,3-c]pyridin-5-yl)-2-methylpropane-2-sulfinamide as off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06-1.12 (m, 9 H) 2.59 (d, J=9.49 Hz, 2 H) 3.03 (s, 2 H) 4.10 (s, 2 H) 6.52 (s, 1 H) 7.10-7.20 (m, 1 H) 7.51-7.59 (m, 1 H) 7.72-7.80 (m, 1 H) 7.93 (d, J=2.45 Hz, 1 H) 8.33-8.40 (m, 1 H).

Workup

  1. customto give a cloudy, light brown solution
  2. stirringthe mixture was stirred for 1 hr
  3. extractionextracted with EtOAc
  4. extractionThe organic extract
  5. washwas washed with saturated NaCl aqueous solution
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude material as a brown solid
  10. customThe crude material was absorbed onto a plug of silica gel
  11. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  12. washeluting with a gradient of 25 to 40 to 80% DCM/MeOH/NH4OH (90:10:1) in 40% EtOAc in heptane

Sources & evidence

ORD record
ord-651391bf448d4333813d119b164d7722
Source dataset
uspto-grants-2016_05
Patent number
US09346827B2

Reaction notes

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