Potassium Phosphate, Tribasic → [4-(5-Bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-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

HRID 1021962Notes

Reaction equation

HRID 1021962 reaction equation
[Br:1][C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6](I)[CH:7]=1.[C:11]([O:14][CH2:15][C:16]1[C:17]([N:25]2[CH2:36][CH2:35][N:34]3[C:27](=[CH:28][C:29]4[CH2:30][C:31]([CH3:38])([CH3:37])[CH2:32][C:33]=43)[C:26]2=[O:39])=[N:18][CH:19]=[CH:20][C:21]=1B(O)O)(=[O:13])[CH3:12].[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].O.C(#N)C>[C:11]([O:14][CH2:15][C:16]1[C:17]([N:25]2[CH2:36][CH2:35][N:34]3[C:27](=[CH:28][C:29]4[CH2:30][C:31]([CH3:38])([CH3:37])[CH2:32][C:33]=43)[C:26]2=[O:39])=[N:18][CH:19]=[CH:20][C:21]=1[C:6]1[CH:7]=[C:2]([Br:1])[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=1)(=[O:13])[CH3:12]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866840253-Bromo-5-iodo-1-methyl-1,2-dihydropyridin-2-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 86684396[4-(5-Bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-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 AcetateYield 22%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
30 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 214b (1.57 g, 5.0 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 (1.98 g, 5.0 mmol), PdCl2(dppf) (205 mg, 0.25 mmol), K3PO4 (2.12 g, 10.0 mmol), Sodium acetate (820 mg, 10.0 mmol), acetonitrile (45 mL), and water (1 mL). The system was evacuated and refilled with N2. The reaction mixture was stirred at 30° C. for 3 h. It was then filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 214c (580 mg, 22%) as a white solid. MS-ESI: [M+H]+ 539.2. 1H NMR (500 MHz, CDCl3) δ 8.49 (d, J=5.0 Hz, 1H), 7.84 (d, J=2.5 Hz, 1H), 7.45 (d, J=2.0 Hz, 1H), 7.09 (d, J=5.0 Hz, 1H), 6.79 (s, 1H), 5.15 (s, 2H), 4.55-4.51 (m, 1H), 4.27-4.25 (m, 1H), 4.15-4.13 (m, 1H), 4.06-4.04 (m, 1H), 3.68 (s, 3H), 2.58-2.56 (m, 2H), 2.51 (s, 2H), 1.86 (s, 3H), 1.28 (s, 6H).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. filtrationIt was then filtered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica-gel column chromatography
  7. washeluting with 30:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-212deb5d4e8e4dfa9568c526686dcdfa
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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