Phosphorus trichloride → N-(6-chloro-pyridin-3-yl)-2-[4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-acetamide

HRID 900097Notes

Reaction equation

HRID 900097 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH:11]2[C:20]3[N:16]([C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18][N:19]=3)[C:15]3[CH:27]=[CH:28][CH:29]=[CH:30][C:14]=3[N:13]([CH2:31][C:32](O)=[O:33])[C:12]2=[O:35])=[CH:2]1.[Cl:36][C:37]1[N:42]=[CH:41][C:40]([NH:43][CH:44]([CH3:46])[CH3:45])=[CH:39][CH:38]=1.P(Cl)(Cl)Cl>C1C=CC=CC=1>[Cl:36][C:37]1[N:42]=[CH:41][C:40]([N:43]([CH:44]([CH3:46])[CH3:45])[C:32](=[O:33])[CH2:31][N:13]2[C:12](=[O:35])[CH:11]([CH2:10][C:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[NH:1][CH:2]=3)[C:20]3[N:16]([C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18][N:19]=3)[C:15]3[CH:27]=[CH:28][CH:29]=[CH:30][C:14]2=3)=[CH:39][CH:38]=1

Participants

5

Reactant 3

HCID 24387Phosphorus trichlorideHCID 589579206-chloro-N-(propan-2-yl)pyridin-3-amineHCID 68607281[4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-acetic acid

Product 1

HCID 58957917N-(6-chloro-pyridin-3-yl)-2-[4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-acetamideYield 13.5%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To a solution of [4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-acetic acid (Preparation 15) (30 mg, 0.06 mmol) and (6-chloro-pyridin-3-yl)-isopropyl-amine (Preparation 2(A)) (10.1 mg, 0.06 mmol) in benzene (2 mL) was added PCl3 (2.0 M in CH2Cl2, 0.1 mL, 0.198 mmol) and the reaction was heated at reflux for 24 hours. The reaction was cooled to room temperature and was diluted with CH2CO2. The organic solution was washed consecutively with aqueous NaHCO3 (1×), water (1×), 1N HCl (1×), and water (1×). The organic solution was dried (MgSO4) and the volatiles were concentrated in vacuo. The residue was purified by medium pressure chromatography eluting with 10% EtOH in CH2Cl2 to yield 5 mg of N-(6-chloro-pyridin-3-yl)-2-[4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-acetamide. 1H NMR (CDCl3) δ 8.26 (s, 1H), 8.17 (s, 1H), 7.76-7.29 (m, 11H), 7.06 (m, 3H), 6.83 (d, 1H), 5.04-4.87 (m, 1H), 4.45-4.15 (m, 1H), 3.94-3.82 (m, 3H), 3.72 (m, 1H), 0.06 (s, 6H); MS 616.6 (M+1), 614.5 (M−1).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 24 hours
  3. additionwas diluted with CH2CO2
  4. washThe organic solution was washed consecutively with aqueous NaHCO3 (1×), water (1×), 1N HCl (1×), and water (1×)
  5. dry with materialThe organic solution was dried (MgSO4)
  6. concentrationthe volatiles were concentrated in vacuo
  7. customThe residue was purified by medium pressure chromatography
  8. washeluting with 10% EtOH in CH2Cl2

Sources & evidence

ORD record
ord-1e2273f0e1be43e488985686623ebf36
Source dataset
uspto-grants-2008_04
Patent number
US07358242B2

Reaction notes

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