Potassium Phosphate, Tribasic → HCID 56971353, compound

HRID 1615512Notes

Reaction equation

HRID 1615512 reaction equation
Cl[C:2]1[S:10][C:9]2[S:8](=[O:12])(=[O:11])[NH:7][CH2:6][C:5]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([OH:13])[C:4]=2[CH:3]=1.[N:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([C:5]2([OH:13])[C:4]3[CH:3]=[C:2]([C:24]4[CH:25]=[CH:26][N:21]=[CH:22][CH:23]=4)[S:10][C:9]=3[S:8](=[O:12])(=[O:11])[NH:7][CH2:6]2)=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 68183049HCID 68183049, compound

Product 1

HCID 56971353HCID 56971353, compoundYield 54.5%

Reagents, catalysts & solvents 1

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst

Procedure

6-chloro-4-(4-chlorophenyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazin-4-ol 1,1-dioxide (0.180 g, 0.514 mmol), pyridine-4-boronic acid (0.126 g, 1.03 mmol), Bis(dibenzylideneacetone)palladium(0) (0.0296 g, 0.0514 mmol), 2-dicyclohexylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (0.0980 g, 0.206 mmol) and Potassium phosphate (0.327 g, 1.54 mmol) were combined in microwave vial and flushed with argon. 1-Butanol (10 mL) was added and the reaction was microwaved on 150 watts, 120° C. for 30 minutes. LCMS indicated the product of coupling. The solvent was evaporated and the residue was purified using column chromatography on silica gel (40 g Analogix column, gradient 10% EA in hexane to 100% EA in hexane over 25 minutes) to give the title compound (110 mg, 52%). LCMS: (FA) ES+ 393, 395. 1H NMR (400 MHz, d6-DMSO) δ: 8.59 (dd, J=4.54, 1.64 Hz, 2H), 8.36 (d, J=0.94 Hz, 1H), 7.68 (dd, J=4.52, 1.68 Hz, 2H), 7.50-7.41 (m, 3H), 6.57 (s, 1H), 7.39-7.27 (m, 2H), 3.75-3.59 (m, 2H).

Workup

  1. customflushed with argon
  2. addition1-Butanol (10 mL) was added
  3. customthe reaction was microwaved on 150 watts, 120° C. for 30 minutes
  4. customThe solvent was evaporated
  5. customthe residue was purified
  6. customon silica gel (40 g Analogix column, gradient 10% EA in hexane to 100% EA in hexane over 25 minutes)

Sources & evidence

ORD record
ord-8e17dea5c6dd46d1baf70dc2cbe4b16f
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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