Nitrogen → HCID 25165894, compound

HRID 1873678Notes

Reaction equation

HRID 1873678 reaction equation
[C:1]1([C@H:13]2[C@H:17]([C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[NH:20][CH:19]=3)[C:16](=O)[NH:15][C:14]2=O)[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1.N#N.[H-].[H-].[H-].[H-].[Li+].[Al+3].O>C1COCC1>[NH:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:18]([C@@H:17]2[CH2:16][NH:15][CH2:14][C@H:13]2[C:1]2[C:11]3=[C:12]4[C:7](=[CH:8][CH:9]=[CH:10]3)[CH2:6][CH2:5][CH2:4][N:3]4[CH:2]=2)=[CH:19]1

Participants

6

Reactant 4

HCID 947NitrogenHCID 962WaterHCID 11494412TivantinibHCID 21226445Aluminium lithium hydride

Product 1

HCID 25165894HCID 25165894, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-pyrrolidine-2,5-dione (WO2006086484A1, 8.34 g, 22.6 mmol) in anhydrous THF (400 mL) was purged with N2 and cooled to 0° C. LiAlH4 (226 mL, 1 M in THF, 226 mmol) was added dropwise. The reaction mixture was stirred at 60° C. overnight. The mixture was cooled with an ice-water bath and water (40 mL) added dropwise under N2 to quench excess LiAlH4. Water (500 mL) was added. The mixture was then acidified with 4M HCl to pH<2. 2M NaOH was added to adjust to pH>9. The mixture was extracted with EtOAc (2×800 mL). The combined EtOAc layer was washed with saturated aqueous NaCl solution, dried over Na2SO4 and concentrated to give 1-[(3R,4R)-4-(1H-indol-3-yl)-pyrrolidin-3-yl]-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline as an orange/yellow solid.

Workup

  1. temperatureThe mixture was cooled with an ice-water bath
  2. customto quench excess LiAlH4
  3. additionWater (500 mL) was added
  4. addition2M NaOH was added
  5. extractionThe mixture was extracted with EtOAc (2×800 mL)
  6. washThe combined EtOAc layer was washed with saturated aqueous NaCl solution
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-4dea6bb89f754b9b8f70f99b559b32f7
Source dataset
uspto-grants-2012_11
Patent number
US08304425B2

Reaction notes

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