Potassium Phosphate, Tribasic → HCID 67309981, compound

HRID 1400551Notes

Reaction equation

HRID 1400551 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[CH:10]=[C:11]([C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)[CH3:12].N1CCC[C@H]1C(O)=O.[CH2:27]([N:30]1[CH2:43][CH2:42][C:33]2[NH:34][C:35]3[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][C:40]=3[C:32]=2[CH2:31]1)[CH:28]=[CH2:29]>C(Cl)Cl.[Cu](I)I.CO.CN(C=O)C>[CH2:27]([N:30]1[CH2:43][CH2:42][C:33]2[N:34]([CH:10]=[C:11]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)[CH3:12])[C:35]3[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][C:40]=3[C:32]=2[CH2:31]1)[CH:28]=[CH2:29]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 68485722HCID 68485722, compoundHCID 86642478(E)-4-(1-bromoprop-1-en-2-yl)pyridine

Product 1

HCID 67309981HCID 67309981, compoundYield 25.7%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

In a 100 mL screw-cap bottle, potassium phosphate tribasic (1.75 g, 8.25 mmol) was taken. 4-(2-Bromo-1-methyl-vinyl)-pyridine (1.1 g, 5.55 mmol) was added under nitrogen at RT. DMF (15 mL) was added and nitrogen was purged into it for 1-2 min. L-proline, (140 mg, 1.21 mmol), copper Iodide (235 mg, 1.21 mmol), and 2-allyl-8-chloro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1 g, 4.06 mmol) were added one by one with nitrogen purging. The screw-cap bottle was closed tightly and the contents heated to 120° C. for 12 h. The reaction was monitored by TLC. The reaction mixture was cooled at RT. DMF was evaporated under vacuum, residue diluted with water (100 mL) and the compound extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (200 mL×3), dried over anhydrous sodium sulfate and concentrated under vacuum to obtain the crude, which was subjected to chromatography (100-200 mesh silica gel and 3% MeOH in DCM as eluent) and recrystallized in ether:hexane (10:90 ratio) to obtain 380 mg of 2-Allyl-8-chloro-5-(2-pyridin-4-yl-propenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole. 1H NMR (CD3OD, HCl salt) δ (ppm): 8.84 (d, 2H), 8.38 (d, 2H), 7.82 (s, 1H), 7.60 (s, 1H), 7.24 (s, 2H), 6.10 (m, 1H), 5.70 (m, 2H), 4.75 (m, 2H), 4.40 (m, 1H), 4.05 (d, 2H), 4.0 (m, 1H), 3.60 (m, 1H), 3.25 (m, 1H), 2.18 (s, 3H).

Workup

  1. customnitrogen was purged into it for 1-2 min
  2. customThe screw-cap bottle was closed tightly
  3. temperatureThe reaction mixture was cooled at RT
  4. customDMF was evaporated under vacuum, residue
  5. additiondiluted with water (100 mL)
  6. extractionthe compound extracted with EtOAc (3×50 mL)
  7. washThe combined organic layers were washed with water (200 mL×3)
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under vacuum
  10. customto obtain the crude, which
  11. customrecrystallized in ether:hexane (10:90 ratio)

Sources & evidence

ORD record
ord-57f2cf285e35418098f4e04bc0f28a41
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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