Ammonia → HCID 10291701, compound

HRID 1816029Notes

Reaction equation

HRID 1816029 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([CH2:10][CH2:11][C:12]([OH:14])=O)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH2:15]1[C:25]2=[C:26]3[C:21](=[CH:22][CH:23]=[CH:24]2)[CH2:20][CH2:19][C:18](=[O:27])[N:17]3[CH2:16]1.N.C1(C)C(CC#N)=CC=CC=1>O>[C:1]([N:4]1[CH2:5][CH2:6][CH:7]([CH2:10][CH2:11][C:12]([C:23]2[CH:22]=[C:21]3[C:26]4=[C:25]([CH2:15][CH2:16][N:17]4[C:18](=[O:27])[CH2:19][CH2:20]3)[CH:24]=2)=[O:14])[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 311552-(o-Tolyl)acetonitrileHCID 91665PyroquilonHCID 98557513-(1-Acetylpiperidin-4-yl)propanoic acid

Product 1

HCID 10291701HCID 10291701, compoundYield 98.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 1-acetyl-4-piperidinepropionic acid (1.99 g, 9.99 mmol), 1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinoline-4-one (1.73 g, 9.99 mmol) and polyphosphoric acid (24 g) was stirred at about 105° C. for 7 hours under nitrogen. Cold water (16 mL) at about 5° C. was slowly added dropwise thereto at −40 to 70° C. and 25% aqueous ammonia was added dropwise thereto at 40 to 50° C. to adjust pH to 8.5. A mixture of toluene-acetonitrile (1:1) (20 mL) was added. The layers were separated, a mixture of toluene-acetonitrile (1:1) (10 mL) was added to the aqueous layer, and the layers were separated. The organic layers were combined, and concentrated to a volume of the solution of ⅕. Diisoporpyl ether (7 mL) was added to the residue to precipitate crystals. The mixture was stirred at about 25° C. for about 1 hour and then at 0 to 5° C. for about 1 hour. Precipitated crystals were separated, washed with diisopropyl ether (3 mL) and dried to obtain 3.47 g (yield 98.6%) of the desired compound as crystals.

Workup

  1. customat 40 to 50° C.
  2. additionwas added
  3. customThe layers were separated
  4. additiona mixture of toluene-acetonitrile (1:1) (10 mL)
  5. additionwas added to the aqueous layer
  6. customthe layers were separated
  7. concentrationconcentrated to a volume of the solution of ⅕
  8. additionDiisoporpyl ether (7 mL) was added to the residue
  9. customto precipitate crystals
  10. stirringThe mixture was stirred at about 25° C. for about 1 hour
  11. waitat 0 to 5° C. for about 1 hour
  12. customPrecipitated crystals
  13. customwere separated
  14. washwashed with diisopropyl ether (3 mL)
  15. customdried

Sources & evidence

ORD record
ord-7455aa78f839463a9a98ef71cf2d7d3a
Source dataset
uspto-grants-2005_04
Patent number
US06881842B2

Reaction notes

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