4-Chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde → HCID 86684187, compound

HRID 592556Notes

Reaction equation

HRID 592556 reaction equation
Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([N:10]2[CH2:22][CH2:21][N:13]3[C:14]4[CH2:15][CH2:16][CH2:17][CH2:18][C:19]=4[CH:20]=[C:12]3[C:11]2=[O:23])[N:5]=[CH:4][CH:3]=1.[CH3:24][N:25]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[C:27]([NH:40][C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([N:47]3[CH2:52][CH2:51][N:50]([CH3:53])[CH2:49][CH2:48]3)[N:42]=2)[C:26]1=[O:54]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCCC1>[CH3:24][N:25]1[C:26](=[O:54])[C:27]([NH:40][C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([N:47]3[CH2:48][CH2:49][N:50]([CH3:53])[CH2:51][CH2:52]3)[N:42]=2)=[CH:28][C:29]([C:2]2[C:7]([CH:8]=[O:9])=[C:6]([N:10]3[CH2:22][CH2:21][N:13]4[C:14]5[CH2:15][CH2:16][CH2:17][CH2:18][C:19]=5[CH:20]=[C:12]4[C:11]3=[O:23])[N:5]=[CH:4][CH:3]=2)=[CH:30]1

Participants

5

Reactant 2

HCID 866841404-Chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehydeHCID 866841882(1H)-Pyridinone, 1-methyl-3-[[6-(4-methyl-1-piperazinyl)-2-pyridinyl]amino]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-

Product 1

HCID 86684187HCID 86684187, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 4-chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino-[1,2-a]indol-2(1H)-yl)nicotinaldehyde 103b (377 mg, 1.15 mmol), 110a (320 mg, 0.78 mmol), Pd(dppf)Cl2 (130 mg, 0.16 mmol), K3PO4.3H2O (52.9 mg, 0.23 mmol), and tetrahydrofuran (20 mL). After three cycles of vacuum/argon flush, the mixture was heated at reflux overnight, cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (40:1) to afford 110b as yellow solid (351 mg, 76%). MS: [M+H]+ 593.

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperaturethe mixture was heated
  4. temperatureat reflux overnight
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with dichloromethane/methanol (40:1)

Sources & evidence

ORD record
ord-365819b97d76462d9bfda7b6eb3ea650
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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