Potassium Phosphate, Tribasic → 2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-[1-methyl-5-({5-methyl-6-oxo-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridine-3-carbaldehyde

HRID 1412072Notes

Reaction equation

HRID 1412072 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[CH2:6][N:5]2[N:9]=[C:10]([NH:12][C:13]3[C:14](=[O:29])[N:15]([CH3:28])[CH:16]=[C:17](B4OC(C)(C)C(C)(C)O4)[CH:18]=3)[CH:11]=[C:4]2[CH2:3]1.Cl[C:31]1[CH:36]=[CH:35][N:34]=[C:33]([N:37]2[CH2:48][CH2:47][C:46]3[C:45]4[CH2:44][C:43]([CH3:50])([CH3:49])[CH2:42][C:41]=4[S:40][C:39]=3[C:38]2=[O:51])[C:32]=1[CH:52]=[O:53].[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>[CH3:49][C:43]1([CH3:50])[CH2:42][C:41]2[S:40][C:39]3[C:38](=[O:51])[N:37]([C:33]4[C:32]([CH:52]=[O:53])=[C:31]([C:17]5[CH:18]=[C:13]([NH:12][C:10]6[CH:11]=[C:4]7[CH2:3][N:2]([CH3:1])[C:7](=[O:8])[CH2:6][N:5]7[N:9]=6)[C:14](=[O:29])[N:15]([CH3:28])[CH:16]=5)[CH:36]=[CH:35][N:34]=4)[CH2:48][CH2:47][C:46]=3[C:45]=2[CH2:44]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866841854-Chloro-2-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}pyridine-3-carbaldehydeHCID 866845665-Methyl-2-(1-methyl-2-oxo-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridin-3-ylamino)-4,5-dihydropyrazolo[1,5-a]pyrazin-6(7H)-one

Product 1

HCID 866845672-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-[1-methyl-5-({5-methyl-6-oxo-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridine-3-carbaldehydeYield 36%

Reagents, catalysts & solvents 3

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

Procedure

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 317a (100 mg, 0.28 mmol), 4-chloro-2-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}pyridine-3-carbaldehyde 109a (112 mg, 0.28 mmol), Pd(dppf)Cl2 (22.9 mg, 0.028 mmol), K3PO4 (118.7 mg, 0.56 mmol), sodium acetate (45.9 mg, 0.56 mmol), water (0.5 mL), and acetonitrile (10 mL). After three cycles of vacuum/argon flush, the mixture was heated at reflux for 1 hour. 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 (50:1 to 30:1) to afford 317b as a yellow solid (60 mg, 36%). MS-ESI: [M+H]+ 597.8.

Workup

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 1 hour
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with dichloromethane/methanol (50:1 to 30:1)

Sources & evidence

ORD record
ord-94991cd9517e4997b5fef7269b62e960
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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