Potassium Phosphate, Tribasic → (E)-2-methyl-5-(2-(pyridin-4-yl)prop-1-enyl)-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401532Notes

Reaction equation

HRID 1401532 reaction equation
[CH3:1][N:2]1[CH2:18][CH2:17][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:12]=3[C:4]=2[CH2:3]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][N:2]1[CH2:18][CH2:17][C:5]2[N:6](/[CH:36]=[C:37](/[C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)\[CH3:38])[C:7]3[CH:8]=[CH:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 67311103HCID 67311103, compoundHCID 86642478(E)-4-(1-bromoprop-1-en-2-yl)pyridine

Product 1

HCID 59454888(E)-2-methyl-5-(2-(pyridin-4-yl)prop-1-enyl)-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 2

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

Conditions

Temperature
140 °C

Procedure

2-Methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (239 mg, 0.94 mmol), and potassium phosphate (399 mg, 1.88 mmol) were mixed in DMF and the suspension was purged with nitrogen. The suspension was heated at 140° C. for 10 min. Copper (I) iodide (17.86 mg, 0.094 mmol) and L-proline (21.64 mg, 0.188 mmol) were added followed by a solution of 4-(1-bromoprop-1-en-2-yl)pyridine (399 mg, 1.88 mmol) in DMF. The contents were purged with nitrogen and heated overnight at 140° C. The contents were cooled to RT and poured into water. The precipitate obtained was filtered, dried and purified by silica gel chromatography (100-200 mesh) eluting with 0-10% MeOH-DCM as eluent. The compound was further purified by HPLC. 1H NMR (CD3OD, TFA salt) δ (ppm): 8.82 (d, 2H), 8.30 (d, 2H), 7.95 (s, 1H), 7.70 (s, 1H), 7.58 (d, 1H), 7.45 (d, 1H), 4.50 (m, 1H), 3.95 (m, 1H), 3.62 (m, 1H), 3.30 (m, 3H), 3.18 (s, 3H), 2.10 (s, 3H).

Workup

  1. customthe suspension was purged with nitrogen
  2. customThe contents were purged with nitrogen
  3. temperatureheated overnight at 140° C
  4. temperatureThe contents were cooled to RT
  5. additionpoured into water
  6. customThe precipitate obtained
  7. filtrationwas filtered
  8. customdried
  9. custompurified by silica gel chromatography (100-200 mesh)
  10. washeluting with 0-10% MeOH-DCM as eluent
  11. customThe compound was further purified by HPLC

Sources & evidence

ORD record
ord-517f60481a324acb85d4f16b1bdc0d78
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

Loading…