Isopropanol → HCID 67004738, compound

HRID 563149Notes

Reaction equation

HRID 563149 reaction equation
[CH2:1]([C@H:8]([N:24]([CH2:39][C:40]1[CH:45]=[CH:44][C:43](Br)=[CH:42][CH:41]=1)[C:25](=[O:38])[CH:26]=[CH:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=1)[C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:47]1[CH:52]=[CH:51][CH:50]=[C:49](B(O)O)[CH:48]=1.C(=O)([O-])[O-].[K+].[K+].C(O)(C)C>C1(C)C=CC=CC=1.O>[CH2:1]([C@H:8]([N:24]([CH2:39][C:40]1[CH:45]=[CH:44][C:43]([C:49]2[CH:48]=[N:47][CH:52]=[CH:51][CH:50]=2)=[CH:42][CH:41]=1)[C:25](=[O:38])[CH:26]=[CH:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=1)[C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 67005310HCID 67005310, compound

Product 1

HCID 67004738HCID 67004738, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

In an inert atmosphere, N—[(S)-1-benzyl-2-(4-benzyl-piperazin-1-yl)-2-oxo-ethyl]-N-(4-bromo-benzyl)-3-(4-trifluoromethyl-phenyl)-acrylamide (60 mg, 0.087 mmol) was dissolved in toluene (0.5 mL) followed by the addition of 3-pyridineboronic acid (11 mg, 0.087 mmol), 2M potassium carbonate solution (0.5 mL) and iso-propanol (0.5 mL). The mixture was degassed with argon for 5 min and heated to 100° C. followed by the addition of tetrakis-(triphenylphosphine)palladium (3 mg, 0.003 mmol). The mixture was stirred for 3 h at 110° C., cooled to rt again and water (1 mL) was added. The product was extracted with EtOAc (3×3 mL). The combined organic layers were evaporated to dryness and the residue was purified by prep. HPLC to give 21 mg (35%) of N—[(S)-1-benzyl-2-(4-benzyl-piperazin-1-yl)-2-oxo-ethyl]-N-(4-pyridin-3-yl-benzyl)-3-(4-trifluoromethyl-phenyl)-acrylamide. LC-MS: tR=0.85 min; [M+H]+=689.68.

Workup

  1. customThe mixture was degassed with argon for 5 min
  2. temperaturecooled to rt again
  3. extractionThe product was extracted with EtOAc (3×3 mL)
  4. customThe combined organic layers were evaporated to dryness
  5. customthe residue was purified by prep

Sources & evidence

ORD record
ord-ba36d065da1d4b76afeb1656512434e3
Source dataset
uspto-grants-2011_11
Patent number
US08067419B2

Reaction notes

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