Ethanol → HCID 10166015, compound

HRID 2180191Notes

Reaction equation

HRID 2180191 reaction equation
[CH:1]1([CH2:4][N:5]2[CH2:10][CH2:9][C:8]([CH2:18][N:19]([CH3:31])[C:20]([NH:22][C:23]3[CH:28]=[C:27]([Cl:29])[CH:26]=[C:25]([Cl:30])[CH:24]=3)=[O:21])([C:11]3[CH:16]=[CH:15][C:14](I)=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.[C:32]([C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1)#[N:33].C([O-])([O-])=O.[Na+].[Na+].CCO>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.O>[C:32]([C:34]1[CH:39]=[C:38]([C:14]2[CH:15]=[CH:16][C:11]([C:8]3([CH2:18][N:19]([CH3:31])[C:20]([NH:22][C:23]4[CH:28]=[C:27]([Cl:29])[CH:26]=[C:25]([Cl:30])[CH:24]=4)=[O:21])[CH2:9][CH2:10][N:5]([CH2:4][CH:1]4[CH2:3][CH2:2]4)[CH2:6][CH2:7]3)=[CH:12][CH:13]=2)[CH:37]=[CH:36][CH:35]=1)#[N:33]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 68530554HCID 68530554, compound

Product 1

HCID 10166015HCID 10166015, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a flask containing 1-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-3-(3,5-dichloro-phenyl)-1-methyl-urea (0.094 g, 0.164 mmol) was added Pd(PPh3)4 (0.02 g, 0.017 mmol, 10 mol %), 3-cyanophenylboronic acid (0.037 g, 0.25 mmol, 1.5 eq.) and Na2CO3 (0.212 g, 2 mmol). The mixture was suspended in toluene (3 mL), EtOH (1.5 mL) and H2O (1 mL) and heated to 80° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (5 mL) and saturated Na2CO3 (5 mL). The organic layer was washed with saturated Na2CO3 (3×5 mL), saturated brine (3×5 mL), dried over anhydrous sodium sulfate, filtered and concentrated by rotary evaporation to give a brown solid which was purified by HPLC to give the title compound 1-[4-(3′-cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-yl methyl]-3-(3,5-dichloro-phenyl)-1-methyl-urea (0.053 g, 60%). 1H NMR (300 MHz, CDCl3): δ 7.95 (s, 1H), 7.92 (d, 1H), 7.79-7.66 (m, 4H), 7.57 (d, 2H), 7.41 (s, 2H), 7.33 (br.s, 1H), 7.06 (s, 1H), 3.76 (m, 2H), 3.63 (s, 1H), 3.60 (s, 2H), 3.08 (s, 3H), 2.87 (br.m, 2H), 2.69 (m, 5H), 1.14 (br.m, 1H), 0.84 (d, 2H), 0.44 (d, 2H)

Workup

  1. custompartitioned between EtOAc (5 mL) and saturated Na2CO3 (5 mL)
  2. washThe organic layer was washed with saturated Na2CO3 (3×5 mL), saturated brine (3×5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customto give a brown solid which
  7. customwas purified by HPLC

Sources & evidence

ORD record
ord-f93f0b5a5dd14e3c9b37e6b3fbde13f3
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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