Acetic Acid → HCID 19900476, compound

HRID 1029724Notes

Reaction equation

HRID 1029724 reaction equation
[CH2:1]([N:4]([C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)[N:5]1[C:13]2[C:8](=[CH:9][C:10]([OH:14])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)[CH2:2][CH3:3].[C:21](N1C=CN=C1)([N:23]1C=CN=C1)=[O:22].C(O)(=O)C.[CH2:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH2:40][CH2:39][NH:38]1>O1CCCC1>[CH2:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH2:40][CH2:39][N:38]1[NH:23][C:21](=[O:22])[O:14][C:10]1[CH:9]=[C:8]2[C:13](=[CH:12][CH:11]=1)[N:5]([N:4]([CH2:1][CH2:2][CH3:3])[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)[CH:6]=[CH:7]2

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 70461,2,3,4-TetrahydroisoquinolineHCID 682631,1'-CarbonyldiimidazoleHCID 18960815HCID 18960815, compound

Product 1

HCID 19900476HCID 19900476, compoundYield 135.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-(propyl-4-pyridinylamino)-1H-indol-5-ol (2.5 g) in 40 ml of tetrahydrofuran was added 1,1'-carbonyldiimidazole (1.83 g) and this mixture was stirred for 24 hours. Then 3.5 ml of glacial acetic acid was added to the reaction mixture. Then 1,2,3,4-tetrahydroisoquinoline (1.49 g) in 10 ml of tetrahydrofuran which had been acidified with 0.60 ml of glacial acetic acid was added to the reaction mixture dropwise. This was stirred for 24 hours and then the reaction mixture was quenched with water, basified with saturated sodium carbonate solution and extracted with ethyl acetate. The organic layer was washed with water and dried (sat. NaCl, anhy. MgSO4). After filtration, the solvent was evaporated to yield an oil (5.6 g) which was eluted with 5% methanol/dichloromethane on a silica gel column via HPLC. The desired fractions were concentrated to yield an oil (4.2 g). This material was dissolved in pentane/ether (1:1), whereupon a solid precipitated out of the solution. This material was collected to yield a solid, 2.6 g, m.p. 141°-143° C.

Workup

  1. additionwas added to the reaction mixture dropwise
  2. stirringThis was stirred for 24 hours
  3. customthe reaction mixture was quenched with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with water
  6. dry with materialdried (sat. NaCl
  7. filtrationAfter filtration
  8. customthe solvent was evaporated

Sources & evidence

ORD record
ord-b81a5e73eb684be58a4351ae3fb4baa2
Source dataset
uspto-grants-1992_04
Patent number
US05102891

Reaction notes

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