Toluene → HCID 25124441, compound

HRID 1890250Notes

Reaction equation

HRID 1890250 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)#[N:2].Br[C:13]1[CH:14]=[C:15]([CH:33]=[CH:34][C:35]=1[CH3:36])[C:16]([NH:18][C:19]1[CH:20]=[N:21][C:22]([N:25]2[CH2:30][CH:29]([CH3:31])[O:28][CH:27]([CH3:32])[CH2:26]2)=[CH:23][CH:24]=1)=[O:17].C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>CCOC(C)=O.O.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>[CH3:32][CH:27]1[O:28][CH:29]([CH3:31])[CH2:30][N:25]([C:22]2[N:21]=[CH:20][C:19]([NH:18][C:16]([C:15]3[CH:14]=[C:13]([C:6]4[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=4)[C:35]([CH3:36])=[CH:34][CH:33]=3)=[O:17])=[CH:24][CH:23]=2)[CH2:26]1

Participants

9

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 66898722HCID 66898722, compound

Product 1

HCID 25124441HCID 25124441, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4-cyanophenyl boronic acid (18 mg, 0.12 mmol), 3-bromo-N-[6-(2,6-dimethyl-morpholin-4-yl)-pyridin-3-yl]-4-methyl-benzamide 8 (40 mg, 0.1 mmol), Pd(PPh3)4 (11 mg, 0.01 mmol), and Na2CO3 (42 mg, 0.4 mmol) in a combined solvent system of toluene (0.2 mL) and water (0.2 mL) and ethanol (0.05 mL) is heated at 140° C. under microwave irradiation for 30 min. The reaction mixture is diluted with EtOAc and water. The aqueous layer is extracted with EtOAc. The combined organic layer is washed with brine and concentrated to give the crude product which is purified by preparative mass triggered HPLC (C18 column, eluted with CH3CN—H2O containing 0.05% TFA) to give 4′-cyano-6-methyl-biphenyl-3-carboxylic acid [6-(2,6-dimethyl-morpholin-4-yl)-pyridin-3-yl]-amide. LC-MS m/z: 427.2 (M+1).

Workup

  1. extractionThe aqueous layer is extracted with EtOAc
  2. washThe combined organic layer is washed with brine
  3. concentrationconcentrated
  4. customto give the crude product which
  5. customis purified by preparative mass
  6. washHPLC (C18 column, eluted with CH3CN—H2O containing 0.05% TFA)

Sources & evidence

ORD record
ord-18960877c8b543329ae302fb68e708ff
Source dataset
uspto-grants-2013_08
Patent number
US08507471B2

Reaction notes

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