Acetic Acid → HCID 66707028, compound

HRID 2041276Notes

Reaction equation

HRID 2041276 reaction equation
[CH2:1]([NH:8][C:9]1[C:19]2[CH2:18][CH2:17][N:16](C([O:22][C:23]([CH3:26])(C)C)=O)[CH2:15][CH2:14][C:13]=2[CH:12]=[CH:11][C:10]=1[Cl:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=[O:29].[C:30]([BH3-])#N.[Na+].[C:34]([OH:37])(=[O:36])[CH3:35]>C(#N)C.CO.O>[C:23]([OH:22])(=[O:29])[CH2:26][CH2:35][C:34]([OH:37])=[O:36].[Cl:27][C:10]1[CH:11]=[CH:12][C:13]2[CH2:14][CH2:15][NH:16][CH2:17][CH2:18][C:19]=2[C:9]=1[N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH3:30]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 66706976HCID 66706976, compound

Product 1

HCID 66707028HCID 66707028, compoundYield 95%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dissolve 6-benzylamino-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (50 mg, 0.11 mmol) in acetonitrile (3 mL) and add a solution of formaldehyde in water (37%, 85 μL, 0.97 mmol) followed by sodium cyanoborohydride (16.5 mg, 0.26 mmol). Heat the solution to reflux 1 h, cool to ambient temperature, add glacial acetic acid (0.25 mL) and stir 72 h. Pour the mixture into water (100 mL) containing methanol (1 mL), extract with DCM (3×20 mL), wash the organic extracts with brine, dry over MgSO4, filter and concentrate in vacuo. Dissolve the resulting residue in DCM (5 mL), and add trifluoroacetic acid (2 mL). Stir for 2 h at ambient temperature and evaporate the solvent. Purify by SCX chromatography. Use a method similar to the General Procedure 2-1 to give the title compound (45 mg, 95%). MS (ES+) m/z: 301 (M+H)+.

Workup

  1. temperatureHeat the solution
  2. temperatureto reflux 1 h
  3. extractionextract with DCM (3×20 mL)
  4. washwash the organic extracts with brine
  5. dry with materialdry over MgSO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. dissolutionDissolve the resulting residue in DCM (5 mL)
  9. additionadd trifluoroacetic acid (2 mL)
  10. stirringStir for 2 h at ambient temperature
  11. customevaporate the solvent
  12. customPurify by SCX chromatography

Sources & evidence

ORD record
ord-0c10319cc33147ca81e82eca641fc1cc
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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