Potassium Phosphate, Tribasic → HCID 86684471, compound

HRID 1411923Notes

Reaction equation

HRID 1411923 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]2[N:10]=[C:11]([NH:13][C:14]3[C:15](=[O:22])[N:16]([CH3:21])[CH:17]=[C:18](Br)[CH:19]=3)[CH:12]=[C:6]2[CH2:5]1)(=[O:3])[CH3:2].[C:23]([O:26][CH2:27][C:28]1[C:29]([N:37]2[C:49](=[O:50])[C:48]3[S:47][C:46]4[CH2:45][CH2:44][CH2:43][CH2:42][C:41]=4[C:40]=3[CH:39]=[N:38]2)=[N:30][CH:31]=[CH:32][C:33]=1B(O)O)(=[O:25])[CH3:24].[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:23]([O:26][CH2:27][C:28]1[C:29]([N:37]2[C:49](=[O:50])[C:48]3[S:47][C:46]4[CH2:45][CH2:44][CH2:43][CH2:42][C:41]=4[C:40]=3[CH:39]=[N:38]2)=[N:30][CH:31]=[CH:32][C:33]=1[C:18]1[CH:19]=[C:14]([NH:13][C:11]2[CH:12]=[C:6]3[CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:9][CH2:8][N:7]3[N:10]=2)[C:15](=[O:22])[N:16]([CH3:21])[CH:17]=1)(=[O:25])[CH3:24]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 580440563-(5-acetyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-5-bromo-1-methylpyridin-2(1H)-oneHCID 86684472HCID 86684472, compound

Product 1

HCID 86684471HCID 86684471, compoundYield 31.2%

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 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 3-(5-acetyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-5-bromo-1-methylpyridin-2(1H)-one 209c (183 mg, 0.50 mmol), {3-[(acetoxy)methyl]-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridin-4-yl}boronic acid 230i (200 mg, 0.50 mmol), Pd(dppf)Cl2 (37 mg, 0.05 mmol), K3PO4 (212 mg, 1.0 mmol), sodium acetate (82 mg, 1.0 mmol), water (0.5 mL), and acetonitrile (5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 90° C. for 1 h. 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 20:1) to afford 247a as yellow solid (100 mg, 31%). MS-ESI: [M+H]+ 641.2.

Workup

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and 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 (50:1 to 20:1)

Sources & evidence

ORD record
ord-a8b8c1ab501f42669ae6d5e56710cab2
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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