Nitrogen → HCID 67814463, compound

HRID 1616819Notes

Reaction equation

HRID 1616819 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH:13][CH2:14][C:15]3[C:16](=[O:23])[NH:17][C:18]([CH3:22])=[CH:19][C:20]=3[CH3:21])=[O:12])[CH:10]=1)[N:7]([CH3:24])[CH:6]=[C:5]2[CH:25]([CH3:27])[CH3:26].C(N(CC)CC)C.N#N>C(O)C.O1CCCC1.C(Cl)Cl.C(Cl)(Cl)Cl>[NH3:7].[CH3:11][OH:12].[CH3:21][C:20]1[CH:19]=[C:18]([CH3:22])[NH:17][C:16](=[O:23])[C:15]=1[CH2:14][NH:13][C:11]([C:9]1[CH:10]=[CH:2][CH:3]=[C:4]2[C:8]=1[N:7]([CH3:24])[CH:6]=[C:5]2[CH:25]([CH3:27])[CH3:26])=[O:12]

Participants

9

Reactant 3

HCID 947NitrogenHCID 8471TriethylamineHCID 57345388HCID 57345388, compound

Product 2

HCID 21705897Ammonia methanolYield 10%HCID 67814463HCID 67814463, compoundYield 185.3%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a dried 50 mL round bottom flask, equipped with a stir bar and H2/N2 inlet was added 10% Pd/C(degussa) (0.025 g, 0.012 mmol). The vessel was degassed with N2 and EtOH (˜0.5 mL) was added. To the slurry was added a solution of 5-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxamide (0.10 g, 0.232 mmol) (solid) in ethanol (6 mL) and hot tetrahydrofuran (THF) (1.0 mL), followed by triethylamine (0.032 mL, 0.232 mmol). The reaction was placed back under N2 and stirred for 5 min, then evacuated/refilled with H2 (3×). The reaction was stirred under a H2 balloon for 4 h. The reaction was then evacuated/refilled with N2 and diluted with DCM (10 mL). A small amount of Celite was added and the reaction stirred for 10 min. The mixture was filtered through analytical grade Celite and washed with successively with 10% MeOH/DCM, EtOH, and DCM. The organics were concentrated and dried on hivac overnight. The residue was dissolved in MeOH/DCM, absorbed onto silica gel, and concentrated in vacuo to dryness. Purification by column chromatography (4 g Isco silica column; Gradient B: 5-85%, A: dichloromethane, B: 10% 2M ammonia/methanol in chloroform) gave N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxamide (77 mg, 0.215 mmol, 92% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.27 (d, J=7.07 Hz, 6H) 2.11 (s, 3H) 2.22 (s, 3H) 3.06-3.19 (m, 1H) 3.65 (s, 3H) 4.33 (d, J=4.80 Hz, 2H) 5.86 (s, 1H) 6.91-6.99 (m, 1H) 6.99-7.08 (m, 2H) 7.59 (dd, J=7.83, 1.26 Hz, 1H) 8.31 (t, J=4.93 Hz, 1H) 11.47 (s, 1H). MS (ES) [M+H]+ 352.4.

Workup

  1. customTo a dried 50 mL round bottom flask, equipped with a stir bar and H2/N2 inlet
  2. customThe vessel was degassed with N2 and EtOH (˜0.5 mL)
  3. additionwas added
  4. additionevacuated/refilled with H2 (3×)
  5. stirringThe reaction was stirred under a H2 balloon for 4 h
  6. additionA small amount of Celite was added
  7. stirringthe reaction stirred for 10 min
  8. filtrationThe mixture was filtered through analytical grade Celite
  9. washwashed with successively with 10% MeOH/DCM, EtOH, and DCM
  10. concentrationThe organics were concentrated
  11. customdried on hivac overnight
  12. dissolutionThe residue was dissolved in MeOH/DCM
  13. customabsorbed onto silica gel
  14. concentrationconcentrated in vacuo to dryness
  15. customPurification by column chromatography (4 g Isco silica column

Sources & evidence

ORD record
ord-0d01a8e5390e452a90b542b7fbb6f093
Source dataset
uspto-grants-2014_07
Patent number
US08765792B2

Reaction notes

Loading…