Cesium carbonate → 2-(4-amino-2-butoxy-6-methylpyridin-3-yl)-4-bromo-N,N-diisopropylbenzamide

HRID 2193001Notes

Reaction equation

HRID 2193001 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:11]([N:13]([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])=[O:12])=[C:6](B(O)O)[CH:7]=1.[CH2:20]([O:24][C:25]1[C:30](I)=[C:29]([NH2:32])[CH:28]=[C:27]([CH3:33])[N:26]=1)[CH2:21][CH2:22][CH3:23].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.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]>[NH2:32][C:29]1[CH:28]=[C:27]([CH3:33])[N:26]=[C:25]([O:24][CH2:20][CH2:21][CH2:22][CH3:23])[C:30]=1[C:6]1[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=1[C:11]([N:13]([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])=[O:12]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 59375409(5-Bromo-2-(diisopropylcarbamoyl)phenyl)boronic acidHCID 593754672-Butoxy-3-iodo-6-methylpyridin-4-amine

Product 1

HCID 593754382-(4-amino-2-butoxy-6-methylpyridin-3-yl)-4-bromo-N,N-diisopropylbenzamide

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of {5-bromo-2-[(diisopropylamino)carbonyl]phenyl}boronic acid (0.26 g, 0.8 mmol) in dioxane (10 mL) was added 2-butoxy-3-iodo-6-methylpyridin-4-amine (0.24 g, 0.8 mmol), Cs2CO3 (0.78 g, 2.4 mmol) and Pd(dppf)Cl2 (40 mg) under a nitrogen atmosphere. The reaction mixture was stirred under reflux for 3 h, and then diluted with water (10 mL). The resulting mixture was extracted with ethyl acetate (20 mL×3). The combined extracts were washed with brine (10 mL), dried over Na2SO4, evaporated. Column chromatography (EtOAc/petroleum ether) was used for purification to afford 2-(4-amino-2-butoxy-6-methylpyridin-3-yl)-4-bromo-N,N-diisopropylbenzamide. 1HNMR (300 MHz, CDCl3) δ 7.50 (dd, J=7.9 Hz, 1.9 Hz, 1H), 7.38 (d, J=1.9 Hz, 1H), 7.13 (d, J=8.3 Hz, 1H), 6.12 (s, 1H), 4.12 (m, 2H), 3.64 (m, 1H), 3.31 (m, 1H), 1.53 (m, 2H), 1.47 (d, J=6.8 Hz, 3H), 1.29 (m, 2H), 1.17 (d, J=6.8 Hz, 3H), 0.99 (d, J=6.8 Hz, 3H), 0.87 (t, J=7.6 Hz, 3H), 0.76 (d, J=6.4 Hz, 3H). LRMS calc'd for (C23H32BrN3O2) [M+H]+, 462; found 462.

Workup

  1. temperatureunder reflux for 3 h
  2. extractionThe resulting mixture was extracted with ethyl acetate (20 mL×3)
  3. washThe combined extracts were washed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customColumn chromatography (EtOAc/petroleum ether) was used for purification

Sources & evidence

ORD record
ord-72a98aab637f425f8580c6aa9bb5c220
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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