Water → Methyl 2-amino-3-(4-(diisopropylcarbamoyl)pyridin-3-yl)benzoate

HRID 1919667Notes

Reaction equation

HRID 1919667 reaction equation
[NH2:1][C:2]1[C:11](Br)=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH:13]([N:16]([CH:28]([CH3:30])[CH3:29])[C:17]([C:19]1[CH:24]=[CH:23][N:22]=[CH:21][C:20]=1B(O)O)=[O:18])([CH3:15])[CH3:14].C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.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]>[NH2:1][C:2]1[C:11]([C:24]2[CH:23]=[N:22][CH:21]=[CH:20][C:19]=2[C:17](=[O:18])[N:16]([CH:28]([CH3:30])[CH3:29])[CH:13]([CH3:14])[CH3:15])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 11615550Methyl 2-amino-3-bromobenzoateHCID 57500682{4-[Di(propan-2-yl)carbamoyl]pyridin-3-yl}boronic acid

Product 1

HCID 50941398Methyl 2-amino-3-(4-(diisopropylcarbamoyl)pyridin-3-yl)benzoateYield 31%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

Methyl 2-amino-3-bromobenzoate (1.0 eq, 652 mg, 2.61 mmol) and 4-(diisopropylcarbamoyl)pyridin-3-ylboronic acid (prepared according to the procedure described in PCT patent application WO2005/105814), 1.0 eq, 600 mg, 2.61 mmol) were combined with cesium carbonate (2.0 eq, 1.699 g, 5.21 mmol) in dioxane containing 5% of water (6 ml). The mixture was degassed by bubbling nitrogen for 10 minutes. PdCl2(dppf) (0.05 eq, 95 mg) was added and the reaction stirred at reflux for 2 hours. Dioxane was evaporated, water was added and the material extracted with CH2Cl2 (3×). The combined extracts were dried over Na2SO4 and the solvents removed in vacuo. The material was purified by flash chromatography on silica gel (eluant 0.5% MeOH in CH2Cl2) to afford methyl 2-amino-3-(4-(diisopropylcarbamoyl)pyridin-3-yl)benzoate as a greenish foam (244 mg, 31% yield). LCMS (ES): >95% pure, m/z 356 [M+1]+.

Workup

  1. customThe mixture was degassed
  2. customby bubbling nitrogen for 10 minutes
  3. temperatureat reflux for 2 hours
  4. customDioxane was evaporated
  5. additionwater was added
  6. extractionthe material extracted with CH2Cl2 (3×)
  7. dry with materialThe combined extracts were dried over Na2SO4
  8. customthe solvents removed in vacuo
  9. customThe material was purified by flash chromatography on silica gel (eluant 0.5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-729cfd02f18b43c4adab11d551cdd678
Source dataset
uspto-grants-2012_05
Patent number
US08168651B2

Reaction notes

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