Ethanol → 4-(5-Cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-[(4'-methylbiphenyl-4-yl)methyl]benzamide

HRID 2090089Notes

Reaction equation

HRID 2090089 reaction equation
Br[C:2]1[CH:31]=[CH:30][C:5]([CH2:6][NH:7][C:8](=[O:29])[C:9]2[CH:14]=[CH:13][C:12]([C:15]3[O:16][C:17]4[C:23]([CH:24]([CH3:26])[CH3:25])=[CH:22][C:21]([C:27]#[N:28])=[CH:20][C:18]=4[N:19]=3)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.C(O)C.[CH3:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([C:21]1[CH:22]=[C:23]([CH:24]([CH3:26])[CH3:25])[C:17]2[O:16][C:15]([C:12]3[CH:13]=[CH:14][C:9]([C:8]([NH:7][CH2:6][C:5]4[CH:30]=[CH:31][C:2]([C:39]5[CH:40]=[CH:41][C:36]([CH3:35])=[CH:37][CH:38]=5)=[CH:3][CH:4]=4)=[O:29])=[CH:10][CH:11]=3)=[N:19][C:18]=2[CH:20]=1)#[N:28]

Participants

9

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 79799Tolylboronic acidHCID 25152389N-(4-Bromobenzyl)-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide

Product 1

HCID 251525794-(5-Cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-[(4'-methylbiphenyl-4-yl)methyl]benzamideYield 33%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of N-(4-bromobenzyl)-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide (30 mg, EXAMPLE 1) in toluene (1 ml), water (0.5 ml), and ethanol (0.25 ml) was added (4-methylphenyl)boronic acid (30 mg), 2M aqueous potassium carbonate (1 ml), and tetrakis(triphenylphosphine)palladium(0) (5 mg). The solution was sealed in a microwave tube and heated to 150° C. for 60 min in a microwave reactor. The mixture was then diluted with ethyl acetate (10 ml) and water (10 ml). The phases were separated and the aqueous phase was extracted with ethyl acetate (10 ml). The combined organic phases were washed with brine (10 ml), dried (sodium sulfate), and concentrated. The residue was purified by flash chromatography on a Biotage Horizon, 25M column, eluting with 1 column volume of 2% ethyl acetate in hexanes, followed by a linear gradient of ethyl acetate in hexanes from 2 to 100% over 10 column volumes to provide the title compound (10 mg, 33%). Mass spectrum (ESI) 486.1 (M+1). NMR (500 MHz, CDCl3): δ 8.34 (s, 1H), 8.32 (s, 1H), 7.99 (s, 1H), 7.98 (s, 1H), 7.93 (d, J=1.5 Hz, 1H), 7.59 (s, 1H), 7.58 (s, 1H), 7.51 (s, 1H), 7.49 (s, 1H), 7.47 (s, 1H), 7.45 (s, 1H), 7.43 (s, 1H), 7.24 (s, 1H), 6.58-6.56 (app t, J=10.5, 1H), 4.72 (d, J=5.5 Hz, 2H), 3.44-3.50 (m, 1H), 2.40 (s, 3H), 1.45 (d, J=6.5 Hz, 6H).

Workup

  1. customThe solution was sealed in a microwave tube
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate (10 ml)
  4. washThe combined organic phases were washed with brine (10 ml)
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on a Biotage Horizon, 25M column
  8. washeluting with 1 column volume of 2% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-551c339627d34cbe928dd9dbc1a1b7d1
Source dataset
uspto-grants-2013_05
Patent number
US08436028B2

Reaction notes

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