Sodium Bicarbonate → HCID 58380744, compound

HRID 1677645Notes

Reaction equation

HRID 1677645 reaction equation
Cl[C:2]1[N:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[C:4]#[N:5].C([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[C:20]([NH2:27])[CH:19]=1)(OC(C)(C)C)=O.[C:28](=[O:31])(O)[O-:29].[Na+]>O1CCOCC1.O>[C:3]([O:29][C:28](=[O:31])[NH:27][C:20]1[CH:19]=[CH:18][C:23]([C:2]2[C:3]([C:4]#[N:5])=[C:6]([Cl:10])[CH:7]=[CH:8][N:9]=2)=[CH:22][CH:21]=1)([CH3:6])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 219978282,4-DichloronicotinonitrileHCID 53442781HCID 53442781, compound

Product 1

HCID 58380744HCID 58380744, compoundYield 161.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 519 mg of 2,4-dichloronicotinonitrile in 25.5 ml of dioxane are added 782 mg of (4-boc-aminophenyl)boronic acid, 693 mg of sodium bicarbonate in 8.5 ml of water and 347 mg of tetrakis(triphenyl-phosphine)palladium. The suspension is stirred at 100° C. for 2 hours under argon. After cooling, the reaction mixture is poured into water and extracted three times with a 90/10 ethyl acetate/methanol solution. The combined organic phases are dried over magnesium sulfate and concentrated under reduced pressure. 1.58 g of crude product are chromatographed on a prepacked Biotage KP-Sil column of 60 Å SiO2 32-63 μm (from 0.5/99.5 to 1/99 gradient of solution A in dichloromethane; solution A=38/17/2 dichloromethane/methanol/aqueous ammonia). 797 mg of [4-(4-chloro-3-cyanopyrid-2-yl)phenyl]carbamic acid tert-butyl ester are obtained, the characteristics of which are as follows:

Workup

  1. temperatureAfter cooling
  2. extractionextracted three times with a 90/10 ethyl acetate/methanol solution
  3. dry with materialThe combined organic phases are dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. custom1.58 g of crude product are chromatographed on a prepacked Biotage KP-Sil column of 60 Å SiO2 32-63 μm (from 0.5/99.5 to 1/99 gradient of solution A in dichloromethane; solution A=38/17/2 dichloromethane/methanol/aqueous ammonia)

Sources & evidence

ORD record
ord-5274f2dbee0b4ffd9ee109db12a26624
Source dataset
uspto-grants-2011_08
Patent number
US08008322B2

Reaction notes

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