Potassium Phosphate, Tribasic → HCID 59454962, compound

HRID 1401567Notes

Reaction equation

HRID 1401567 reaction equation
[CH3:1][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][OH:18])[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:36]=[C:37]([C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=1)[CH3:38]>CN(C=O)C.[Cu]I>[CH3:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:36]=[C:37](/[C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)\[CH3:38])[C:6]3[CH2:11][CH2:12][N:13]([CH2:15][CH2:16][CH2:17][OH:18])[CH2:14][C:5]=3[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 67310539HCID 67310539, compoundHCID 86642478(E)-4-(1-bromoprop-1-en-2-yl)pyridine

Product 1

HCID 59454962HCID 59454962, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
85 °C

Procedure

3-(3,4-Dihydro-8-methyl-1H-pyrido[4,3-b]indol-2(5H)-yl)propan-1-ol (500 mg, 2.04 mmol) was dissolved in DMF (10 mL) and to this solution were added potassium phosphate (865 mg, 4.08 mmol), copper(I) iodide (38.76 mg, 0.204 mmol) and L-proline (46.92 mg, 0.408 mmol). The reaction mixture was stirred for 10 min. and 4-(1-bromoprop-1-en-2-yl)pyridine (600 mg, 3.06 mmol) in DMF (2 mL) was added dropwise. The reaction mixture was purged with nitrogen and heated overnight at 85° C. (prolonged heating was required some cases). DMF was evaporated; the residue was diluted with water and filtered. The solid was purified by silica gel chromatography (100-200 mesh, neutralized by aq. ammonia) eluting with 0-10% MeOH-DCM. The compound was further purified by HPLC. 1H NMR (CD3OD, di-HCl salt) δ (ppm): 8.70 (m, 2H), 7.98 (m, 2H), 7.56 (s, 1H), 7.38 (s, 1H), 7.10 (m, 2H), 4.40 (m, 1H), 4.0 (m, 1H), 3.78 (t, 2H), 3.60 (m, 1H), 3.50 (t, 2H), 3.40-3.20 (m, 3H), 2.42 (s, 3H), 2.15 (m, 2H), 2.10 (s, 3H).

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. temperatureprolonged heating
  3. customDMF was evaporated
  4. additionthe residue was diluted with water
  5. filtrationfiltered
  6. customThe solid was purified by silica gel chromatography (100-200 mesh, neutralized by aq. ammonia)
  7. washeluting with 0-10% MeOH-DCM
  8. customThe compound was further purified by HPLC

Sources & evidence

ORD record
ord-8020c621aebf40f69900dbdb60392212
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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