Triethylamine → cis-5-Methoxy-1-[4-(6-methylpyridin-2-yl)-1-naphthylaminocarbonyl]-6-(3,4,5-trimethylpiperazin-1-yl)indoline

HRID 352373Notes

Reaction equation

HRID 352373 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](C(O)=O)=[CH:10][CH:9]=2)[CH:5]=[CH:4][CH:3]=1.C([N:23]([CH2:26]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:35])C=CC=CC=1.[CH3:45][O:46][C:47]1[CH:48]=[C:49]2[C:53](=[CH:54][C:55]=1[N:56]1[CH2:61][C@H:60]([CH3:62])[N:59]([CH3:63])[C@H:58]([CH3:64])[CH2:57]1)[NH:52][CH2:51][CH2:50]2>C1(C)C=CC=CC=1.C(Cl)Cl>[CH3:45][O:46][C:47]1[CH:48]=[C:49]2[C:53](=[CH:54][C:55]=1[N:56]1[CH2:57][C@H:58]([CH3:64])[N:59]([CH3:63])[C@H:60]([CH3:62])[CH2:61]1)[N:52]([C:26]([NH:23][C:11]1[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:8]([C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=3)=[CH:9][CH:10]=1)=[O:35])[CH2:51][CH2:50]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 227118464-(6-Methylpyridin-2-yl)-1-naphthoic acidHCID 69836129cis-5-Methoxy-6-(3,4,5-trimethylpiperazin-1-yl)indoline

Product 1

HCID 69836264cis-5-Methoxy-1-[4-(6-methylpyridin-2-yl)-1-naphthylaminocarbonyl]-6-(3,4,5-trimethylpiperazin-1-yl)indolineYield 52.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred mixture of D13 (87 mg, 0.33 mmole), triethylamine (40 mg, 0.40 mmole) and diphenylphosphoryl azide (96 mg, 0.35 mmole) in toluene was heated at reflux under argon for 0.5 h, then allowed to cool to room temperature and treated with a solution of D3 (70 mg, 0.25 mmole) in DCM (10 ml). The mixture was stirred at room temperature for 4 h, then treated with polystyrene bound trisamine (80 mg of 3.6 mmole/g) and polystyrene bound methylisocyanate (60 mg of 1.2 mmole/g) and stirred at room temperature for 70 h, then filtered through Kieselguhr. The filtrate was washed with 10% Na2CO3 solution, dried (Na2SO4), concentrated under vacuum and purified by chromatography on basic alumina eluting with EtOAc, followed by trituration with Et2O to afford the title compound as a yellow solid (70 mg, 52%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux under argon for 0.5 h
  3. stirringstirred at room temperature for 70 h
  4. filtrationfiltered through Kieselguhr
  5. washThe filtrate was washed with 10% Na2CO3 solution
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under vacuum
  8. custompurified by chromatography on basic alumina eluting with EtOAc

Sources & evidence

ORD record
ord-9c15c80b24134ffbb31e44ae69f45395
Source dataset
uspto-grants-2004_06
Patent number
US06747030B1

Reaction notes

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