Potassium Phosphate, Tribasic → (2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{1-methyl-5-[(1-methyl-1H-imidazol-4-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl Acetate

HRID 1022101Notes

Reaction equation

HRID 1022101 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:12]=[CH:13][N:14]([CH3:16])[CH:15]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:17]([O:20][CH2:21][C:22]1[C:23]([N:37]2[CH2:48][CH2:47][N:46]3[C:39](=[CH:40][C:41]4[CH2:42][C:43]([CH3:50])([CH3:49])[CH2:44][C:45]=43)[C:38]2=[O:51])=[N:24][CH:25]=[CH:26][C:27]=1B1OC(C)(C)C(C)(C)O1)(=[O:19])[CH3:18].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>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(#N)C.O>[C:17]([O:20][CH2:21][C:22]1[C:23]([N:37]2[CH2:48][CH2:47][N:46]3[C:39](=[CH:40][C:41]4[CH2:42][C:43]([CH3:50])([CH3:49])[CH2:44][C:45]=43)[C:38]2=[O:51])=[N:24][CH:25]=[CH:26][C:27]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:12]=[CH:13][N:14]([CH3:16])[CH:15]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:19])[CH3:18]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839805-Bromo-1-methyl-3-(1-methyl-1H-imidazol-4-ylamino)pyridin-2(1H)-oneHCID 86684419(2-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

Product 1

HCID 86684508(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{1-methyl-5-[(1-methyl-1H-imidazol-4-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl AcetateYield 94.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 268c (150 mg, 0.53 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 (80.4 mg, 0.21 mmol), Pd(dppf)Cl2 (17.2 mg, 0.021 mmol), K3PO4 (89 mg, 0.42 mmol), sodium acetate (57.1 mg, 0.42 mmol), water (0.2 mL), and acetonitrile (10 mL). After three cycles of vacuum/argon flush, the mixture was heated at 90° C. for 2.5 hrs. 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 dichloromethane/methanol (30:1 to 20:1) to afford 268d (110 mg, 37.2%) as brown solid. MS-ESI: [M+H]+ 556.4.

Workup

  1. customA 50-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica-gel column chromatography
  7. washeluting with dichloromethane/methanol (30:1 to 20:1)

Sources & evidence

ORD record
ord-0c256dd650c441b5b83a4c68923d43d6
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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