Acetonitrile → 2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(6-{imidazo[1,2-a]pyridin-7-ylamino}-4-methyl-5-oxopyrazin-2-yl)pyridine-3-carbaldehyde

HRID 592773Notes

Reaction equation

HRID 592773 reaction equation
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([NH:10][C:11]3[C:12](=[O:21])[N:13]([CH3:20])[CH:14]=[C:15](B(O)O)[N:16]=3)=[CH:6][C:5]=12.Cl[C:23]1[CH:28]=[CH:27][N:26]=[C:25]([N:29]2[CH2:40][CH2:39][N:38]3[C:31](=[CH:32][C:33]4[CH2:34][C:35]([CH3:42])([CH3:41])[CH2:36][C:37]=43)[C:30]2=[O:43])[C:24]=1[CH:44]=[O:45].C([O-])(=O)C.[K+].C(#N)C>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].O>[CH3:41][C:35]1([CH3:42])[CH2:34][C:33]2[CH:32]=[C:31]3[N:38]([CH2:39][CH2:40][N:29]([C:25]4[C:24]([CH:44]=[O:45])=[C:23]([C:15]5[N:16]=[C:11]([NH:10][C:7]6[CH:8]=[CH:9][N:4]7[CH:3]=[CH:2][N:1]=[C:5]7[CH:6]=6)[C:12](=[O:21])[N:13]([CH3:20])[CH:14]=5)[CH:28]=[CH:27][N:26]=4)[C:30]3=[O:43])[C:37]=2[CH2:36]1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 517044Potassium AcetateHCID 768540784-chloro-2-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta(4,5)pyrrolo(1,2-a)pyrazin-2-yl)nicotinaldehydeHCID 866843326-(Imidazo[1,2-a]pyridin-7-ylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-ylboronic Acid

Product 1

HCID 866843332-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(6-{imidazo[1,2-a]pyridin-7-ylamino}-4-methyl-5-oxopyrazin-2-yl)pyridine-3-carbaldehydeYield 29.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A 100-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 185b (400 mg, 1.40 mmol), 4-chloro-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-3-carbaldehyde 108a (192 mg, 0.56 mmol), potassium acetate (220 mg, 2.24 mmol), acetonitrile (20 mL), and water (0.5 mL). After bubbling nitrogen through the suspension for 30 minutes, 1,1′-bis(diphenylphosphino)Ferrocenedichloropalladium(II) (49 mg, 0.054 mmol) was added. The system was subjected to three cycles of vacuum/argon flush and heated at 80° C. for 3 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×20 mL). The combined filtrate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (40:1 to 10:1) to afford 185c (90 mg, 29%) as a light yellow solid. MS-ESI: [M+H]+ 549

Workup

  1. customA 100-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 30 minutes
  3. customflush
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. washThe solid was washed with dichloromethane (2×20 mL)
  7. concentrationThe combined filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica-gel column chromatography
  9. washeluting with dichloromethane/methanol (40:1 to 10:1)

Sources & evidence

ORD record
ord-844ab73cada1480bb799a8e2c05c0789
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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