Acetamidine monohydrochloride → 2-methyl-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepine

HRID 1965942Notes

Reaction equation

HRID 1965942 reaction equation
C[O-].[Na+].Cl.[C:5]([NH2:8])(=[NH:7])[CH3:6].C([N:16]1[CH2:22][CH2:21][CH:20](Br)[C:19](=O)[CH2:18][CH2:17]1)C1C=CC=CC=1>CO>[CH3:6][C:5]1[NH:8][C:19]2[CH2:18][CH2:17][NH:16][CH2:22][CH2:21][C:20]=2[N:7]=1

Participants

5

Reactant 3

HCID 67170Acetamidine monohydrochlorideHCID 10942334Sodium Methoxide2×HCID 20803026N-benzyl-5-bromohexahydro-4-azepinone

Product 1

HCID 210803132-methyl-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3 equivalents (4.463 g) of sodium methoxide are placed in MeOH at ambient temperature, 7.8 g of acetamidine-hydrochloride are added and the mixture is stirred for 30 min. Then 10 g of N-benzyl-5-bromohexahydro-4-azepinone are added. After another 30 minutes an additional 2 eq. (2.976 g) of sodium methoxide are added to the mixture which is refluxed for 11 hours. After cooling to ambient temperature the mixture is fully concentrated by evaporation in vacuo, the material remaining is triturated with about 140 ml of isopropanol, filtered and the filtrate is evaporated down again. The crude product is taken up in 50 ml of 1N K2CO3 solution and extracted 3× with 40 ml of CH2Cl2. The organic phases are dried with MgSO4, filtered off and evaporated to dryness. The residue is chromatographed over silica gel (CH2Cl2/MeOH=87:13 to 70:30). Yield: 1.7 g

Workup

  1. temperatureis refluxed for 11 hours
  2. concentrationis fully concentrated by evaporation in vacuo
  3. customthe material remaining is triturated with about 140 ml of isopropanol
  4. filtrationfiltered
  5. customthe filtrate is evaporated down again
  6. extractionextracted 3× with 40 ml of CH2Cl2
  7. dry with materialThe organic phases are dried with MgSO4
  8. filtrationfiltered off
  9. customevaporated to dryness
  10. customThe residue is chromatographed over silica gel (CH2Cl2/MeOH=87:13 to 70:30)

Sources & evidence

ORD record
ord-3a98d5461a264998bdb359ccb5b89afb
Source dataset
uspto-grants-2013_04
Patent number
US08420630B2

Reaction notes

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