Acetone → 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-(4-{3-[4-(trifluoromethyl)phenyl]pyrrolidin-1-yl}benzyl)benzamide

HRID 2090090Notes

Reaction equation

HRID 2090090 reaction equation
CC(C)([O-])C.[Na+].Br[C:8]1[CH:37]=[CH:36][C:11]([CH2:12][NH:13][C:14](=[O:35])[C:15]2[CH:20]=[CH:19][C:18]([C:21]3[O:22][C:23]4[C:29]([CH:30]([CH3:32])[CH3:31])=[CH:28][C:27]([C:33]#[N:34])=[CH:26][C:24]=4[N:25]=3)=[CH:17][CH:16]=2)=[CH:10][CH:9]=1.[F:38][C:39]([F:52])([F:51])[C:40]1[CH:45]=[CH:44][C:43]([CH:46]2[CH2:50][CH2:49][NH:48][CH2:47]2)=[CH:42][CH:41]=1.CC(C)=O>C1(C)C=CC=CC=1>[C:33]([C:27]1[CH:28]=[C:29]([CH:30]([CH3:32])[CH3:31])[C:23]2[O:22][C:21]([C:18]3[CH:19]=[CH:20][C:15]([C:14]([NH:13][CH2:12][C:11]4[CH:36]=[CH:37][C:8]([N:48]5[CH2:49][CH2:50][CH:46]([C:43]6[CH:44]=[CH:45][C:40]([C:39]([F:38])([F:51])[F:52])=[CH:41][CH:42]=6)[CH2:47]5)=[CH:9][CH:10]=4)=[O:35])=[CH:16][CH:17]=3)=[N:25][C:24]=2[CH:26]=1)#[N:34]

Participants

6

Reactant 4

HCID 180AcetoneHCID 38657063-[4-(Trifluoromethyl)phenyl]pyrrolidineHCID 23676156Sodium t-butoxideHCID 25152389N-(4-Bromobenzyl)-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide

Product 1

HCID 251525814-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-(4-{3-[4-(trifluoromethyl)phenyl]pyrrolidin-1-yl}benzyl)benzamideYield 53%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

Sodium tert-butoxide (10 mg), N-(4-bromobenzyl)-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide (24 mg, EXAMPLE 1), and 3-[4-(trifluoromethyl)phenyl]pyrrolidine (31 mg) were dissolved in toluene (5.0 mL). To this mixture was added bispalladiumtribenzylidene acetone (10 mg) and 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphine) (12 mg). The mixture was heated to 150° C. for 25 min in a microwave reactor. Upon cooling, the mixture was then concentrated in vacuo, taken up in dichloromethane, and purified via flash chromatography on a Biotage Horizon, 40 M column, eluting with 1 column volume of 100% hexanes, followed by a linear gradient of ethyl acetate in hexanes from 0 to 100% over 10 column volumes, followed by 4 column volumes of 100% ethyl acetate to provide the title compound (16 mg, 53%). Mass spectrum (ESI) 609.1 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.31 (d, J=8.5 Hz, 2H), 7.95 (d, J=8.5 Hz, 2H), 7.94 (s, 1H), 7.59 (d, J=8.0 Hz, 2H), 7.51 (s, 1H), 7.39 (d, J=8.0 Hz, 2H), 7.29 (d, J=8.4 Hz, 2H), 6.60 (d, J=8.4 Hz, 2H), 6.33 (t, J=4.0 Hz, 1H), 4.59 (d, J=5.3 Hz, 2H), 3.75 (t, J=8.4 Hz, 1H), 3.57 (m, 5H), 2.47 (m, 1H), 2.15 (m, 1H), 1.46 (d, J=6.9, 6H).

Workup

  1. temperatureUpon cooling
  2. concentrationthe mixture was then concentrated in vacuo
  3. custompurified via flash chromatography on a Biotage Horizon, 40 M column
  4. washeluting with 1 column volume of 100% hexanes

Sources & evidence

ORD record
ord-92869a864f2d4f8ea00278af31199514
Source dataset
uspto-grants-2013_05
Patent number
US08436028B2

Reaction notes

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