Trifluoroacetic acid → HCID 58465875, compound

HRID 931593Notes

Reaction equation

HRID 931593 reaction equation
[NH2:1][C:2]1([CH:18]([CH3:21])[CH2:19][OH:20])[C:15]2[CH:14]=[C:13]([Cl:16])[N:12]=[CH:11][C:10]=2[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:17])=[CH:6][CH:7]=2.C([O-])(=O)C.[Na+].[N:27]#[C:28]Br.C(O)(C(F)(F)F)=O>CCO.C(Cl)Cl>[Br:17][C:5]1[CH:4]=[C:3]2[C:2]3([CH:18]([CH3:21])[CH2:19][O:20][C:28]([NH2:27])=[N:1]3)[C:15]3[CH:14]=[C:13]([Cl:16])[N:12]=[CH:11][C:10]=3[O:9][C:8]2=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10476Cyanogen Bromide2×HCID 517045Sodium Acetate2×HCID 86761965HCID 86761965, compound

Product 1

HCID 58465875HCID 58465875, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-(5-amino-7-bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-yl)propan-1-ol (0.85 g, 2.300 mmol) in EtOH (10 mL) was added anhydrous sodium acetate (0.377 g, 4.60 mmol) followed by the drop wise addition of cyanogen bromide (3.0M in CH2Cl2; 0.920 mL, 2.76 mmol). The suspension was stirred at RT for 48 h. Additional cyanogen bromide (0.8 mL, 0.6 eq) and NaOAc (180 mg, 1.0 eq) were added. The reaction mixture was allowed to stir for 3 days at RT. The reaction mixture was concentrated under reduced pressure, washed with water and extracted with DCM. The combined organic layers were dried over MgSO4 and azeotropically dried with toluene. A white solid was obtained which was suspended in DCM (15 mL). Upon dropwise addition of TFA (2 mL) the reaction mixture turned clear and yellow. The resulting mixture was stirred at RT for 20 min. The solvent was removed under reduced pressure and aqueous saturated NaHCO3 solution and CH2Cl2 were added. The suspension was filtered and 7-bromo-3-chloro-5′-methyl-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazin]-2′-amine was obtained as a white solid (305 mg). The filtrate was transferred into a separatory funnel. The organic phase was separated and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography to obtain additional 7-bromo-3-chloro-5′-methyl-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazin]-2′-amine (300 mg).

Workup

  1. stirringto stir for 3 days at RT
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. washwashed with water
  4. extractionextracted with DCM
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. dry with materialazeotropically dried with toluene
  7. customA white solid was obtained which
  8. stirringThe resulting mixture was stirred at RT for 20 min
  9. customThe solvent was removed under reduced pressure and aqueous saturated NaHCO3 solution and CH2Cl2
  10. additionwere added
  11. filtrationThe suspension was filtered

Sources & evidence

ORD record
ord-fd90919551804aa9bd7599a8057b3aa7
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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