m-Chloroperbenzoic acid → HCID 89422459, compound

HRID 1752409Notes

Reaction equation

HRID 1752409 reaction equation
[N:1]1([C:6]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)=[CH:14][CH:13]=3)[N:9]=[C:8]([C:26]([NH2:28])=[O:27])[CH:7]=2)[CH2:5][CH:4]=[CH:3][CH2:2]1.C1C=C(Cl)C=C(C(OO)=[O:37])C=1>C(Cl)Cl>[CH:4]12[O:37][CH:3]1[CH2:2][N:1]([C:6]1[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)=[CH:14][CH:13]=3)[N:9]=[C:8]([C:26]([NH2:28])=[O:27])[CH:7]=1)[CH2:5]2

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acid5×HCID 71285469HCID 71285469, compound

Product 1

HCID 89422459HCID 89422459, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of the 6-(2,5-dihydro-1H-pyrrol-1-yl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide (0.333 g, 0.885 mmol) in DCM (25 mL) was added mCPBA (0.201 g, 0.897 mmol, 77% solid). After 2 h, more mCPBA was added (0.198 g, 0.883 mmol, 77% solid). After stirring overnight, more mCPBA was added (0.202 g, 0.901 mmol, 77% solid) and the reaction was heated to reflux. After 5 h, more mCPBA was added (0.200 g, 0.892 mmol, 77% solid). After 2 h, more mCPBA was added (0.202 g, 0.901 mmol, 77% solid) and refluxing was continued overnight. When cooled, the reaction mixture was diluted with 100 mL DCM, washed twice with 25 mL saturated aqueous NaHCO3 solution, and once with 25 mL brine. The organic layers were dried over MgSO4, filtered, and evaporated to a residue. The residue was chromatographed over silica gel with 25-75% acetone in hexanes. The product fractions were evaporated in vacuo and the resulting solid triturated with 1 mL acetone, filtered, rinsed once with 0.5 mL acetone and dried under vacuum at 40° C. to give 6-(6-oxa-3-azabicyclo[3.1.0]hexan-3-yl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide as an off-white powder (0.052 g, 0.13 mmol, 15% yield). LC/MS: m/z=393.2 [M+H]+.

Workup

  1. temperaturethe reaction was heated to reflux
  2. waitAfter 5 h
  3. waitAfter 2 h
  4. temperaturerefluxing
  5. waitwas continued overnight
  6. temperatureWhen cooled
  7. washwashed twice with 25 mL saturated aqueous NaHCO3 solution
  8. dry with materialThe organic layers were dried over MgSO4
  9. filtrationfiltered
  10. customevaporated to a residue
  11. customThe residue was chromatographed over silica gel with 25-75% acetone in hexanes
  12. customThe product fractions were evaporated in vacuo
  13. customthe resulting solid triturated with 1 mL acetone
  14. filtrationfiltered
  15. washrinsed once with 0.5 mL acetone
  16. customdried under vacuum at 40° C.

Sources & evidence

ORD record
ord-50ac753a57db412db08d5e11676ae65c
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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