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-6-yl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]pyridin-3-yl)methyl Acetate

HRID 1021923Notes

Reaction equation

HRID 1021923 reaction equation
BrC1N=C(N[C:11]2[CH:16]=[CH:15][N:14]3[CH:17]=[CH:18][N:19]=[C:13]3[CH:12]=2)C(=O)N(C)C=1.[C:20]([O:23][CH2:24][C:25]1[C:26]([N:34]2[CH2:45][CH2:44][N:43]3[C:36](=[CH:37][C:38]4[CH2:39][C:40]([CH3:47])([CH3:46])[CH2:41][C:42]=43)[C:35]2=[O:48])=[N:27][CH:28]=[CH:29][C:30]=1B(O)O)(=[O:22])[CH3:21].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:57](#[N:59])[CH3:58]>O.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]>[C:20]([O:23][CH2:24][C:25]1[C:26]([N:34]2[CH2:45][CH2:44][N:43]3[C:36](=[CH:37][C:38]4[CH2:39][C:40]([CH3:47])([CH3:46])[CH2:41][C:42]=43)[C:35]2=[O:48])=[N:27][CH:28]=[CH:29][C:30]=1[C:57]1[N:59]=[C:36]([NH:43][C:16]2[CH:11]=[CH:12][C:13]3[N:14]([CH:17]=[CH:18][N:19]=3)[CH:15]=2)[C:35](=[O:48])[N:34]([CH3:26])[CH:58]=1)(=[O:22])[CH3:21]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 62657Potassium Phosphate, TribasicHCID 866843315-Bromo-3-(imidazo[1,2-a]pyridin-7-ylamino)-1-methylpyrazin-2(1H)-oneHCID 86684340[4-(Dihydroxyboranyl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetate

Product 1

HCID 86684377(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-6-yl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]pyridin-3-yl)methyl AcetateYield 34%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A 25-mL single-neck round-bottomed flask equipped with a reflux condenser was charged with 201a (64 mg, 0.20 mmol), {3-[(acetyloxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (160 mg, 0.40 mmol), Pd(dppf)Cl2 (10 mg, 0.012 mmol), K3PO4 (100 mg, 0.39 mmol), NaOAc.3H2O (60 mg, 0.44 mmol), water (6 drops), and acetonitrile (5 mL). The system was evacuated and refilled with N2. The reaction mixture was stirred at 100° C. for 2 h. It was then 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 20:1 dichloromethane/methanol to afford 201b (40 mg, 34%) as a yellow brown solid. MS-ESI: [M+H]+ 593.2.

Workup

  1. customA 25-mL single-neck round-bottomed flask equipped with a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with 20:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-fc8103307d0243ce9ac9e14d05bec611
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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