Potassium Phosphate, Tribasic → HCID 59455128, compound

HRID 1400544Notes

Reaction equation

HRID 1400544 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH2:15][CH2:16][CH2:17][CH:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[OH:19])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.Br[CH:44]=[C:45]([C:47]1[CH:52]=[CH:51][N:50]=[CH:49][CH:48]=1)[CH3:46]>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:44]=[C:45](/[C:47]3[CH:52]=[CH:51][N:50]=[CH:49][CH:48]=3)\[CH3:46])[C:6]3[CH2:11][CH2:12][N:13]([CH2:15][CH2:16][CH2:17][CH:18]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)[OH:19])[CH2:14][C:5]=3[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 67310169HCID 67310169, compoundHCID 86642478(E)-4-(1-bromoprop-1-en-2-yl)pyridine

Product 1

HCID 59455128HCID 59455128, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

4-(8-Chloro-3,4-dihydro-1H-pyrido[4,3-b]indol-2(5H)-yl)-1-(4-fluorophenyl)butan-1-ol (200 mg, 0.538 mmol) was dissolved in DMF (5 mL). potassium phosphate (457 mg, 2.15 mmol), copper (I) iodide (10.22 mg, 0.054 mmol) and L-proline (12.4 mg, 0.108 mmol) were added, followed by addition of 4-(1-bromoprop-1-en-2-yl)pyridine (158.1 mg, 0.806 mmol). Nitrogen gas was purged for 2 min and the reaction mixture was heated at 85° C. overnight (prolonged heating required in some cases). DMF was evaporated, water (20 mL) added and the compound extracted with EtOAc (3×50 mL). The organic layer was washed with water (2×50 mL) and the desired compound purified through silica gel (100-200 mesh) using 0-10% MeOH:DCM as eluent. It was further purified through reverse phase HPLC. Yield: 5.4 mg (di HCL salt). 1H NMR (CD3OD, Di-HCl salt) δ (ppm): 8.85 (d, 2H), 8.38 (d, 2H), 7.82 (s, 1H), 7.62 (s, 1H), 7.42 (t, 2H), 7.30 (s, 2H), 7.10 (t, 2H), 4.78 (m, 3H), 4.40 (m, 1H), 3.95 (m, 1H), 3.60 (m, 1H), 3.45 (t, 2H), 3.20 (m, 1H), 2.18 (s, 3H), 2.10-1.85 (m, 4H).

Workup

  1. customNitrogen gas was purged for 2 min
  2. temperatureprolonged heating
  3. customDMF was evaporated
  4. additionwater (20 mL) added
  5. extractionthe compound extracted with EtOAc (3×50 mL)
  6. washThe organic layer was washed with water (2×50 mL)
  7. customthe desired compound purified through silica gel (100-200 mesh)
  8. customIt was further purified through reverse phase HPLC

Sources & evidence

ORD record
ord-d0678fad8cbe412a83b95920ba732560
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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