4-Bromoaniline → HCID 90010431, compound

HRID 1056606Notes

Reaction equation

HRID 1056606 reaction equation
[CH2:1]([C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([NH:15]C(=O)OC(C)(C)C)=[CH:11][CH:10]=2)=[CH:7][C:6]([C:23]2[O:24][C:25](=[O:29])[N:26]([CH3:28])[N:27]=2)=[CH:5][N:4]=1)[CH3:2].CC1(C)C(C)(C)OB(C2C=CC(NC(=O)OC(C)(C)C)=CC=2)O1.BrC1C=CC(N)=CC=1>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([C:8]2[CH:7]=[C:6]([C:23]3[O:24][C:25](=[O:29])[N:26]([CH3:28])[N:27]=3)[CH:5]=[N:4][C:3]=2[CH2:1][CH3:2])=[CH:10][CH:11]=1

Participants

6

Reactant 3

HCID 78074-BromoanilineHCID 2734617tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamateHCID 118027069HCID 118027069, compound

Product 1

HCID 90010431HCID 90010431, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

Step-1: tert-Butyl (4-(2-ethyl-5-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyridin-3-yl)phenyl)carbamate: To a solution of Intermediate-1a (2.30 g, 8.10 mmol, 1.0 eq) and tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (2.58 g, 8.10 mmol, 1.0 eq; prepared from 4-bromoaniline by following the procedure described in organic and biomolecular chemistry, 2010, 8 (15), 3457) in dioxane (25 mL) was added Pd(PPh3)2Cl2 (284 mg, 0.40 mmol). The resulting mixture was thoroughly deoxygenated by subjecting to vacuum/nitrogen cycle three times and the reaction mixture was heated to 75° C. and further maintained for 15 h under nitrogen atmosphere. The resulting mixture was cooled to RT and filtered through celite. The filtrate was concentrated under vacuum and the crude product was purified by flash column chromatography (silica gel, ethyl acetate-hexanes system as eluent) to afford 2.80 g (78%) of the desired compound as a white solid. 1HNMR (400 MHz, CDCl3) δ 8.96 (s, 1H), 7.89 (s, 1H), 7.48 (d, J=8.0 Hz, 2H), 7.26 (d, J=8.0 Hz, 2H), 6.75 (s, 1H), 3.51 (s, 3H), 2.84 (q, J=7.0 Hz, 2H), 1.58 (s, 9H), 1.23 (t, J=7.0 Hz, 3H); ESI-MS (m/z) 397 (MH)+

Workup

  1. customThe resulting mixture was thoroughly deoxygenated
  2. temperaturefurther maintained for 15 h under nitrogen atmosphere
  3. temperatureThe resulting mixture was cooled to RT
  4. filtrationfiltered through celite
  5. concentrationThe filtrate was concentrated under vacuum
  6. customthe crude product was purified by flash column chromatography (silica gel, ethyl acetate-hexanes system as eluent)

Sources & evidence

ORD record
ord-31077a964a184177aff226773858d219
Source dataset
uspto-grants-2016_07
Patent number
US09399638B2

Reaction notes

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