Dimethylformamide → HCID 178481325, compound

HRID 1284446Notes

Reaction equation

HRID 1284446 reaction equation
[CH3:1][N:2]1[C@@H:11]([C:12]([OH:14])=O)[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:15].C1CCC(N=C=NC2CCCCC2)CC1.CN(C=O)C.[NH2:36][C@H:37]([C:44]([N:46]1[CH2:53][CH2:52][CH2:51][C@H:47]1[C:48]([NH2:50])=[O:49])=[O:45])[CH2:38][C:39]1[N:43]=[CH:42][NH:41][CH:40]=1>C(N(CC)CC)C>[O:15]=[C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:10][C@@H:11]([C:12]([NH:36][C@H:37]([C:44]([N:46]2[CH2:53][CH2:52][CH2:51][C@H:47]2[C:48]([NH2:50])=[O:49])=[O:45])[CH2:38][C:39]2[N:43]=[CH:42][NH:41][CH:40]=2)=[O:14])[N:2]1[CH3:1]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10868DicyclohexylcarbodiimideHCID 42109032HCID 42109032, compoundHCID 178513962HCID 178513962, compound

Product 1

HCID 178481325HCID 178481325, compoundYield 47.6%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

A solution of (3R)-2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (350 mg), DCC (412 mg) and DMF (8 ml) is stirred at 9° C. for 1.5 hours, and L-histidyl-L-prolinamide.2HBr (702 mg) and triethylamine (0.49 ml) are added thereto. The mixture is stirred for 2 days. Insoluble materials are filtered off, and the filtrate is distilled under reduced pressure to remove DMF. The residue is dissolved in an aqueous sodium bicarbonate solution, and the solution is passed through a column (2.4×21 cm) packed with CHP-20P resin. The column is washed with water (one liter), and the product is eluted with 30% methanol. The fractions positive to Pauly reagent are collected, and the collection solution is distilled to remove methanol. The residue is lyophilized, whereby Nα -[(3S)-1-oxo-2-methyl-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]-L-histidyl-L-prolinamide (370 mg) is obtained. Yield: 47.6%

Workup

  1. filtrationInsoluble materials are filtered off
  2. distillationthe filtrate is distilled under reduced pressure
  3. customto remove DMF
  4. dissolutionThe residue is dissolved in an aqueous sodium bicarbonate solution
  5. washThe column is washed with water (one liter)
  6. washthe product is eluted with 30% methanol
  7. customThe fractions positive to Pauly reagent are collected
  8. distillationthe collection solution is distilled
  9. customto remove methanol

Sources & evidence

ORD record
ord-287a361b36614893949c77623ca1f2ea
Source dataset
uspto-grants-1986_01
Patent number
US04563306

Reaction notes

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