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-({5-[1-(oxetan-3-yl)azetidin-3-yl]pyridin-2-yl}amino)-6-oxopyridin-3-yl]pyridin-3-yl)methyl Acetate

HRID 593042Notes

Reaction equation

HRID 593042 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:20][N:19]([CH:21]4[CH2:24][O:23][CH2:22]4)[CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:25]([O:28][CH2:29][C:30]1[C:31]([N:39]2[CH2:50][CH2:49][N:48]3[C:41](=[CH:42][C:43]4[CH2:44][C:45]([CH3:52])([CH3:51])[CH2:46][C:47]=43)[C:40]2=[O:53])=[N:32][CH:33]=[CH:34][C:35]=1B(O)O)(=[O:27])[CH3:26].C([O-])(=O)C.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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(#N)C>[C:25]([O:28][CH2:29][C:30]1[C:31]([N:39]2[CH2:50][CH2:49][N:48]3[C:41](=[CH:42][C:43]4[CH2:44][C:45]([CH3:52])([CH3:51])[CH2:46][C:47]=43)[C:40]2=[O:53])=[N:32][CH:33]=[CH:34][C:35]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:20][N:19]([CH:21]4[CH2:24][O:23][CH2:22]4)[CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:27])[CH3:26]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 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 acetateHCID 866845135-Bromo-1-methyl-3-(5-(1-(oxetan-3-yl)azetidin-3-yl)pyridin-2-ylamino)pyridine-2(1H)-one

Product 1

HCID 86684514(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-({5-[1-(oxetan-3-yl)azetidin-3-yl]pyridin-2-yl}amino)-6-oxopyridin-3-yl]pyridin-3-yl)methyl AcetateYield 49.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A 25-ml round-bottomed flask equipped with a reflux condenser was charged with 272a (140 mg, 0.35 mmol), {3-[(acetoxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diaza-tricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (140 mg, 0.35 mmol), Pd(dppf)Cl2 (28 mg, 0.035 mmol), sodium acetate (58 mg, 0.70 mmol), K3PO4 (148 mg, 0.70 mmol), water (6 drops), and acetonitrile (6 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 2 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 25:1 dichloromethane/methanol to afford 272b (114 mg, 46%) as a brown solid. MS-ESI: [M+H]+ 664.4

Workup

  1. customA 25-ml round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 25:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-0feff68656164bc3b679316ea07428b0
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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