Hydrochloric Acid → HCID 86728102, compound

HRID 627629Notes

Reaction equation

HRID 627629 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@:9]([NH:21]S(C(C)(C)C)=O)([CH3:20])[CH2:10][S:11]([C:14]2([C:18]#[N:19])[CH2:17][CH2:16][CH2:15]2)(=[O:13])=[O:12])[C:5]([F:8])=[N:6][CH:7]=1.Cl.C(OCC)C>CO>[NH2:21][C@@:9]([C:4]1[C:5]([F:8])=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=1)([CH3:20])[CH2:10][S:11]([C:14]1([C:18]#[N:19])[CH2:17][CH2:16][CH2:15]1)(=[O:13])=[O:12]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 86728101HCID 86728101, compound

Product 1

HCID 86728102HCID 86728102, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of N—((R)-2-(5-bromo-2-fluoropyridin-3-yl)-1-((1-cyanocyclobutyl)sulfonyl)propan-2-yl)-2-methylpropane-2-sulfinamide (7.0 g, 14.57 mmol) in MeOH (10 mL) was added hydrogen chloride, 1 m in diethyl ether (58.3 ml, 58.3 mmol) and stirred at room temperature for 30 min until starting material was consumed. The mixture was concentrated, diluted with DCM and neutralized with 10% Na2CO3 and 1 N NaOH. The organic phase was dried over Na2SO4, filtered and concentrated to afford a pale yellow oil as (R)-1-((2-amino-2-(5-bromo-2-fluoropyridin-3-yl)propyl)sulfonyl)cyclobutanecarbonitrile. This product was dissolved in DCE (40 mL), placed in a water bath at room temperature and trimethylaluminum solution, 2.0M in toluene (11.66 ml, 23.31 mmol) was added dropwise. After the addition was completed, the water bath was removed and the resulting mixture was stirred at room temperature for 17 h. The mixture was cooled to 0° C. and 1N aqueous hydrochloric acid (43.7 ml, 43.7 mmol) was added dropwise via an addition funnel (slowly at first until vigorous reaction subsided) and stirred at room temperature. The aqueous solution was extracted with DCM. The pH of the aq. phase was adjusted to pH>10 with 10 N NaOH and extracted with DCM. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-100% EtOAc/hexanes to afford a light yellow solid as (R)-9-amino-7-(5-bromo-2-fluoropyridin-3-yl)-7-methyl-5-thia-8-azaspiro[3.5]non-8-ene 5,5-dioxide (3.9 g, 10.37 mmol, 71.1% yield). LC/MS (ESI+) m/z=375.6 (M+H).

Workup

  1. customwas consumed
  2. concentrationThe mixture was concentrated
  3. additiondiluted with DCM and neutralized with 10% Na2CO3 and 1 N NaOH
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-d6bfa40054b8490fb3fa0b1374004a1a
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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