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

HRID 2090088Notes

Reaction equation

HRID 2090088 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[CH:7]([O:10][C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][C:12]=1B(O)O)([CH3:9])[CH3:8].Br[C:22]1[CH:51]=[CH:50][C:25]([CH2:26][NH:27][C:28](=[O:49])[C:29]2[CH:34]=[CH:33][C:32]([C:35]3[O:36][C:37]4[C:43]([CH:44]([CH3:46])[CH3:45])=[CH:42][C:41]([C:47]#[N:48])=[CH:40][C:38]=4[N:39]=3)=[CH:31][CH:30]=2)=[CH:24][CH:23]=1.O>C1(C)C=CC=CC=1.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(O)C>[C:47]([C:41]1[CH:42]=[C:43]([CH:44]([CH3:46])[CH3:45])[C:37]2[O:36][C:35]([C:32]3[CH:33]=[CH:34][C:29]([C:28]([NH:27][CH2:26][C:25]4[CH:50]=[CH:51][C:22]([C:12]5[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:11]=5[O:10][CH:7]([CH3:9])[CH3:8])=[CH:23][CH:24]=4)=[O:49])=[CH:30][CH:31]=3)=[N:39][C:38]=2[CH:40]=1)#[N:48]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 35474222-Isopropoxy-5-methylphenylboronic acidHCID 25152389N-(4-Bromobenzyl)-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide

Product 1

HCID 251523904-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-[(2'-isopropoxy-5'-methylbiphenyl-4-yl)methyl]benzamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

Sodium carbonate (100 μl of a 2M aqueous solution), (2-isopropoxy-5-methylphenyl)boronic acid (19 mg), and N-(4-bromobenzyl)-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide (24 mg, EXAMPLE 1) were dissolved in toluene (2.1 ml), water (0.6 ml) and ethanol (0.3 ml). To this solution was added tetrakis(triphenylphosphine)palladium(0) (9 mg). The mixture was heated to 150° C. for 25 min via microwave. Upon cooling, the mixture was concentrated in vacuo and then dissolved in dichloromethane (5 ml). The sample was transferred to a Biotage 40M column and purified via flash chromatography, eluting 1 column volume of 100% hexanes followed by a gradient of 0 to 100% ethyl acetate in hexanes over 10 column volume, followed by 100% ethyl acetate for 4 column volumes, to provide the title compound. Mass spectrum (ESI) 544.2 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.35 (d, J=8.4 Hz, 2H), 8.00 (d, J=8.2 Hz, 2H), 7.94 (s, 1H), 7.58 (d, J=8.0 Hz, 2H), 7.52 (s, 1H), 7.40 (d, J=8.0 Hz, 2H), 7.13 (s, 1H), 7.09 (d, J=8.2 Hz, 1H), 6.90 (d, J=8.4 Hz, 2H), 6.47 (t, J=4.6 Hz, 1H), 4.73 (d, J=5.5 Hz, 3H), 4.40 (sept, J=6.2 Hz, 1H), 3.48 (sept, J=7.1 Hz, 1H), 2.32 (s, 3H), 1.46 (d, J=6.9, 6H), 1.24 (d, J=5.9, 6H).

Workup

  1. temperatureUpon cooling
  2. concentrationthe mixture was concentrated in vacuo
  3. dissolutiondissolved in dichloromethane (5 ml)
  4. custompurified via flash chromatography
  5. washeluting 1 column volume of 100% hexanes

Sources & evidence

ORD record
ord-97b7c0f296fb4b48b72a6907de84b639
Source dataset
uspto-grants-2013_05
Patent number
US08436028B2

Reaction notes

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