3-Iodotoluene → N-[1-(2-phenylethyl)-5-(2-methylphenyl)-4-ethoxycarbonylpyrazol-3-yl]-N-[(2'-(N-triphenylmethyl-(1H-tetrazol-5-yl))biphenyl-4-yl)methyl]-n-propylamine

HRID 357905Notes

Reaction equation

HRID 357905 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[CH3:6][CH2:7]CCCC.C1([CH2:18][CH2:19][N:20]2[C:24](Br)=[C:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:22]([N:31]([CH2:69][CH2:70][CH3:71])[CH2:32][C:33]3[CH:38]=[CH:37][C:36]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=4[C:45]4[N:49]([C:50]([C:63]5[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=5)([C:57]5[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=5)[C:51]5[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=5)[N:48]=[N:47][N:46]=4)=[CH:35][CH:34]=3)=[N:21]2)C=CC=CC=1.C(=O)=O.CC(C)=O.I[C:80]1[CH:81]=[C:82]([CH3:86])[CH:83]=[CH:84][CH:85]=1.[Cl-].[NH4+]>[Cl-].[Zn+2].[Cl-].C1COCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd].C1COCC1.CN1CCCN(C)C1=O>[C:4]1([CH2:18][CH2:19][N:20]2[C:24]([C:83]3[CH:84]=[CH:85][CH:80]=[CH:81][C:82]=3[CH3:86])=[C:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:22]([N:31]([CH2:69][CH2:70][CH3:71])[CH2:32][C:33]3[CH:34]=[CH:35][C:36]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=4[C:45]4[N:49]([C:50]([C:51]5[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=5)([C:57]5[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=5)[C:63]5[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=5)[N:48]=[N:47][N:46]=4)=[CH:37][CH:38]=3)=[N:21]2)[CH:7]=[CH:6][CH:1]=[CH:2][CH:3]=1

Participants

10

Reactant 5

HCID 122683-IodotolueneHCID 25517Ammonium ChlorideHCID 18522661Acetone cardiceHCID 22103828N-[1-(2-phenylethyl)-4-ethoxycarbonyl-5-bromopyrazol-3-yl]-N-[(2'-(N-triphenylmethyl-(1H-tetrazol-5-yl))biphenyl-4-yl)methyl]-n-propylamineHCID 178418244HCID 178418244, compound

Product 1

HCID 22103833N-[1-(2-phenylethyl)-5-(2-methylphenyl)-4-ethoxycarbonylpyrazol-3-yl]-N-[(2'-(N-triphenylmethyl-(1H-tetrazol-5-yl))biphenyl-4-yl)methyl]-n-propylamine

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 66790640zinc chloride THFCatalystHCID 8028TetrahydrofuranSolvent3×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

0.23 ml of 1.6M n-butyl lithium/hexane solution were dropwise added to THF solution (5 ml) containing 208 mg of N-[1-(2-phenylethyl)-5-bromo-4-ethoxycarbonylpyrazol-3-yl]-N-[(2'-(N-triphenylmethyl-(1H-tetrazol-5-yl))biphenyl-4-yl)methyl]-n-propylamine and 0.04 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone and stirred for 10 minutes, while cooling with dry ice-acetone. 0.74 ml of 0.5M zinc chloride/THF solution were added thereto and stirred for 30 minutes at room temperature. Then, THF solution (5 ml) containing 83 mg of m-iodotoluene and 36 mg of tetrakis(triphenylphosphine) palladium(O) were added thereto and stirred for 28 hours at 60° C. 10 ml of ammonium chloride were added to the reaction solution, THF was distilled off under reduced pressure, and the resultant was extracted with 50 ml of dichloromethane. After dried over magnesium sulfate, the solvent was distilled off under reduced pressure. The resulting residue was subjected to silica gel column chromatography (n-hexane-ethyl acetate=5:1) to obtain 171 mg of the intended compound as a pale yellow, amorphous solid.

Workup

  1. stirringstirred for 30 minutes at room temperature
  2. additionwere added
  3. stirringstirred for 28 hours at 60° C
  4. distillationwas distilled off under reduced pressure
  5. extractionthe resultant was extracted with 50 ml of dichloromethane
  6. dry with materialAfter dried over magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-36c1056e31c540b39b50cde6d859cf28
Source dataset
uspto-grants-1998_11
Patent number
US05840909

Reaction notes

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