Potassium Phosphate, Tribasic → HCID 89690465, compound

HRID 1481847Notes

Reaction equation

HRID 1481847 reaction equation
Cl[C:2]1[CH:19]=[C:18]([N:20]2[CH2:25][CH2:24][N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[CH3:32])[CH2:22][CH2:21]2)[C:17]([N+:33]([O-:35])=[O:34])=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][CH2:8][CH2:9][N:10]1[CH2:14][CH2:13][CH2:12][C:11]1=[O:15])=[O:5].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:44]1(B(O)O)[CH2:46][CH2:45]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C(OCC)(=O)C.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CO>[CH:44]1([C:2]2[CH:19]=[C:18]([N:20]3[CH2:25][CH2:24][N:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[CH3:32])[CH2:22][CH2:21]3)[C:17]([N+:33]([O-:35])=[O:34])=[CH:16][C:3]=2[C:4]([NH:6][CH2:7][CH2:8][CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:15])=[O:5])[CH2:46][CH2:45]1

Participants

11

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 89690627HCID 89690627, compound

Product 1

HCID 89690465HCID 89690465, compoundYield 80%

Reagents, catalysts & solvents 6

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

2-Chloro-5-nitro-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide 1f (200.0 mg, 0.40 mmol, 100 mol %), potassium phosphate tribasic (169.8 mg, 0.80 mmol, 200 mol %), cyclopropylboronic acid (41.2 mg, 0.48 mmol, 120 mol %), tricyclohexylphosphine (11.2 mg, 0.04 mmol, 10 mol %), and palladium(II) acetate (4.5 mg, 0.02 mmol, 5 mol %) were combined in de-gassed toluene (4.0 ml) and 200 mL of water was added. The vessel was sealed and heated to 100° C. for 3 h and then the reaction was cooled and diluted with water and ethyl acetate. The suspension was filtered through a pad of Celite and the mixture was extracted twice with ethyl acetate and the combined organic extracts were dried over sodium sulfate and concentrated. Column chromatography (dichloromethane to 10% methanol in dichloromethane) afforded 2-cyclopropyl-5-nitro-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide 5a (161.0 mg; 0.32 mmol; 79.6%) as an amorphous yellow solid. LCMS (ESI) 506 (M+H).

Workup

  1. customThe vessel was sealed
  2. temperaturethe reaction was cooled
  3. filtrationThe suspension was filtered through a pad of Celite
  4. extractionthe mixture was extracted twice with ethyl acetate
  5. dry with materialthe combined organic extracts were dried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-17df6a7f262044eea6f32b45059044f8
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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