Hydrochloric Acid → HCID 86715891, compound

HRID 627648Notes

Reaction equation

HRID 627648 reaction equation
[NH2:1][C@@:2]([C:13]1[C:14]([F:20])=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=1)([CH3:12])[CH2:3][S:4]([C:7]([CH3:11])([CH3:10])[C:8]#[N:9])(=[O:6])=[O:5].C[Al](C)C.Cl>ClCCCl>[NH2:9][C:8]1[C:7]([CH3:10])([CH3:11])[S:4](=[O:6])(=[O:5])[CH2:3][C@:2]([C:13]2[C:14]([F:20])=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=2)([CH3:12])[N:1]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 16682925TrimethylaluminumHCID 86728114HCID 86728114, compound

Product 1

HCID 86715891HCID 86715891, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of N#R)-2-(5-bromo-2-fluoropyridin-3-yl)-1-((2-cyanopropan-2-yl)sulfonyl)propan-2-yl)-2-methylpropane-2-sulfinamide (1.63 g, 3.48 mmol) in methanol (25 mL) was added hydrogen chloride (4.0 M in 1,4-dioxane, 4.35 mL, 17.4 mmol) and stirred at room temperature for 40 min until the starting material was consumed. The mixture was concentrated, diluted with DCM, and neutralized with 10% aqueous Na2CO3 and 1 M NaOH. The organic phase was dried over Na2SO4, filtered, and concentrated to afford (R)-2-((2-amino-2-(5-bromo-2-fluoropyridin-3-yl)propyl)sulfonyl)-2-methylpropanenitrile as a pale yellow oil. The (R)-2-((2-amino-2-(5-bromo-2-fluoropyridin-3-yl)propyl)sulfonyl)-2-methylpropanenitrile was dissolved in 1,2-dichloroethane (100 mL) and trimethylaluminum (2 M in toluene, 2.78 mL, 5.57 mmol) was added dropwise. The resulting mixture was stirred at room temperature for 17 h. The mixture was cooled to 0° C. and hydrochloric acid (1 M, 17.40 mL, 17.40 mmol) was added dropwise via an addition funnel (slowly at first until the vigorous reaction subsided) and stirred at room temperature. The aqueous solution was extracted with DCM. The pH of the aqueous phase was adjusted to pH>10 with 10 M NaOH and extracted with DCM. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (eluted with 0-100% EtOAc/hexanes) gave (R)-5-amino-3-(5-bromo-2-fluoropyridin-3-yl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide (1.0 g, 2.8 mmol, 79% yield) as a light yellow solid. LC/MS (ESI) m/z=364 (M+H).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. customfirst until the vigorous reaction
  3. stirringstirred at room temperature
  4. extractionThe aqueous solution was extracted with DCM
  5. extractionextracted with DCM
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash column chromatography on silica gel (eluted with 0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-bb913b492719491881da8d2a80b7a993
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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