2-(Di-tert-butylphosphino)biphenyl → (S)-2-sec-butylamino-6-methanesulfonylamino-isonicotinic acid methyl ester

HRID 732365Notes

Reaction equation

HRID 732365 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40].[Na]>C1(C)C=CC=CC=1.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]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([NH:42][S:39]([CH3:38])(=[O:41])=[O:40])[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1

Participants

6

Reactant 3

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 86614996HCID 86614996, compoundHCID 86614997HCID 86614997, compound

Product 1

HCID 68814626(S)-2-sec-butylamino-6-methanesulfonylamino-isonicotinic acid methyl esterYield 46.4%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
99 °C

Procedure

Add to a 300 mL of autoclave reactor (s)-(+)-2-sec-butylamino-6-chloro-isonicotinic acid methyl ester (12.46 g, 0.05134 mol), bis(dibenzylideneacetone)-palladium (0) (2.35 g, 0.002567 mol), 2-di-tert-butylphosphino biphenyl (1.53 g, 0.005134 mol) and sodium methanesulfonamide (12.02 g, 0.1027 mol) in toluene (250 mL). Flush with nitrogen 3 times and heat to 99° C. for 24 h. Filter and dissolve the filter cake in water (400 mL). Extract the aqueous layer with chloroform (3×200 mL), dry (magnesium sulfate) and concentrate. Dissolve the crude product in dichloromethane (20 mL) and precipitate out by adding hexanes (400 mL) to give a solid (7.18 g, 46%). m.p. 118.6-123.0° C., 1H NMR (500 MHz, DMSO) δ 6.87 (s, 1H), 6.69 (s, 1H), 4.83 (br, 1H), 3.94 (s, 3H), 3.74 (m, 1H), 3.27 (s, 1H), 1.60 (m, 2H) 1.25 (d, J=7 Hz, 3H), 0.99 (t, J=7 Hz, 3H).

Workup

  1. customFlush with nitrogen 3 times
  2. filtrationFilter
  3. dissolutiondissolve the filter cake in water (400 mL)
  4. extractionExtract the aqueous layer with chloroform (3×200 mL)
  5. dry with materialdry (magnesium sulfate)
  6. concentrationconcentrate
  7. dissolutionDissolve the crude product in dichloromethane (20 mL)
  8. customprecipitate out
  9. additionby adding hexanes (400 mL)

Sources & evidence

ORD record
ord-667f43aa396140229fc88d6a0f4ecf80
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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