Ammonia → HCID 10291701, compound

HRID 1816026Notes

Reaction equation

HRID 1816026 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.C1(C)C(CC#N)=CC=CC=1.N>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 85.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 2.5 kg of 1-acetyl-4-piperidinepropionic acid, 2.17 kg (1 equivalent) of 1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinoline-4-one and 26.0 kg of polyphosphoric acid was stirred at about 105° C. for 8 hours under nitrogen and 13 L of cold water at about 5° C. was slowly added dropwise thereto while maintaining about 70° C. Further, 25 L of a mixture of toluene-acetonitrile (1:1) was added at about 55° C. and pH was adjusted to about 8.5 by adding 25% aqueous ammonia solution (about 50 L) while maintaining about 55° C. The layers were separated, 10 L of a mixture of toluene-acetonitrile (1:1) 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 about 10 L. To the residue was added 9 L of isopropyl ether at about 20° C. to precipitate crystals. The mixture was stirred at about 20° C. for about 1.5 hours and then at about 5° C. for about 1.5 hours. Precipitated crystals were separated, washed with about 6 L of a mixture of isopropyl ether-ethyl acetate (1:1) cooled to about 5° C., and 10 L of isopropyl ether cooled to about 5° C., and dried to obtain 3.78 kg (yield 85%) of the desired compound as crystals.

Workup

  1. temperaturewhile maintaining about 70° C
  2. temperaturewhile maintaining about 55° C
  3. customThe layers were separated
  4. addition10 L of a mixture of toluene-acetonitrile (1:1) was added to the aqueous layer
  5. customthe layers were separated
  6. concentrationconcentrated to a volume of the solution of about 10 L
  7. additionTo the residue was added 9 L of isopropyl ether at about 20° C.
  8. customto precipitate crystals
  9. stirringThe mixture was stirred at about 20° C. for about 1.5 hours
  10. waitat about 5° C. for about 1.5 hours
  11. customPrecipitated crystals
  12. customwere separated
  13. washwashed with about 6 L of a mixture of isopropyl ether-ethyl acetate (1:1)
  14. temperaturecooled to about 5° C.
  15. temperature10 L of isopropyl ether cooled to about 5° C.
  16. customdried

Sources & evidence

ORD record
ord-79dd62a6a5914a00ba41a77663c03b3b
Source dataset
uspto-grants-2005_04
Patent number
US06881842B2

Reaction notes

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