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-{5-[(5-ethyl-1,3,4-thiadiazol-2-yl)amino]-1-methyl-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl Acetate

HRID 593174Notes

Reaction equation

HRID 593174 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[S:12][C:13]([CH2:16][CH3:17])=[N:14][N:15]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:18]([O:21][CH2:22][C:23]1[C:24]([N:38]2[CH2:49][CH2:48][N:47]3[C:40](=[CH:41][C:42]4[CH2:43][C:44]([CH3:51])([CH3:50])[CH2:45][C:46]=43)[C:39]2=[O:52])=[N:25][CH:26]=[CH:27][C:28]=1B1OC(C)(C)C(C)(C)O1)(=[O:20])[CH3:19].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(O[Na])=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].O.C(#N)C>[C:18]([O:21][CH2:22][C:23]1[C:24]([N:38]2[CH2:49][CH2:48][N:47]3[C:40](=[CH:41][C:42]4[CH2:43][C:44]([CH3:51])([CH3:50])[CH2:45][C:46]=43)[C:39]2=[O:52])=[N:25][CH:26]=[CH:27][C:28]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[S:12][C:13]([CH2:16][CH3:17])=[N:14][N:15]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:20])[CH3:19]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 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 acetateHCID 86684602HCID 86684602, compoundHCID 178418247HCID 178418247, compound

Product 1

HCID 86684603(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{5-[(5-ethyl-1,3,4-thiadiazol-2-yl)amino]-1-methyl-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl AcetateYield 48.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 332a (200 mg, 0.63 mmol), {3-[(acetoxy)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 (754 mg, 1.89 mmol), PdCl2(dppf) (51 mg, 0.063 mmol), K3PO4 (267 mg, 1.26 mmol), CH3COONa (103 mg, 1.26 mmol), acetonitrile (15 mL), and water (0.5 mL). After bubbling nitrogen through the resulting mixture for 20 minutes, it was heated at 100° C. under a nitrogen atmosphere for 2 h. The resulting mixture was cooled to room temperature and filtered. The filtrate was evaporated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 332b as a brown solid (178 mg, 48%). MS-ESI: [M+H]+ 588.2

Workup

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the resulting mixture for 20 minutes
  3. temperatureThe resulting mixture was cooled to room temperature
  4. filtrationfiltered
  5. customThe filtrate was evaporated under reduced pressure
  6. customthe residue was purified by silica-gel column chromatography
  7. washeluting with 50:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-093102431d92425fbea8b25d85689b71
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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