Diisopropylethylamine → 4-(tert-butyldimethylsilyloxy)-N1-(6-indolylcarbonyl)-N2-[1-(4-pyridyl)piperidin-4-yl]methoxycarbonyl-1,2-benzenediamine

HRID 2301839Notes

Reaction equation

HRID 2301839 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([OH:12])=O)[CH:8]=2)[CH:3]=[CH:2]1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(C(C)C)CC)(C)C.[Si:46]([O:53][C:54]1[CH:55]=[C:56]([NH:61][C:62]([O:64][CH2:65][CH:66]2[CH2:71][CH2:70][N:69]([C:72]3[CH:77]=[CH:76][N:75]=[CH:74][CH:73]=3)[CH2:68][CH2:67]2)=[O:63])[C:57]([NH2:60])=[CH:58][CH:59]=1)([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47].C(=O)([O-])O.[Na+]>C(Cl)Cl.CN(C)C=O>[Si:46]([O:53][C:54]1[CH:55]=[C:56]([NH:61][C:62]([O:64][CH2:65][CH:66]2[CH2:71][CH2:70][N:69]([C:72]3[CH:73]=[CH:74][N:75]=[CH:76][CH:77]=3)[CH2:68][CH2:67]2)=[O:63])[C:57]([NH:60][C:10]([C:7]2[CH:8]=[C:9]3[C:4]([CH:3]=[CH:2][NH:1]3)=[CH:5][CH:6]=2)=[O:12])=[CH:58][CH:59]=1)([C:49]([CH3:52])([CH3:50])[CH3:51])([CH3:48])[CH3:47]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 5952301H-indole-6-carboxylic acidHCID 2733179PyBroPHCID 538609714-(tert-Butyldimethyl-silyloxy)-N2-[1-(4-pyridyl)piperidin-4-yl]methoxycarbonyl-1,2-benzenediamine

Product 1

HCID 155430414-(tert-butyldimethylsilyloxy)-N1-(6-indolylcarbonyl)-N2-[1-(4-pyridyl)piperidin-4-yl]methoxycarbonyl-1,2-benzenediamineYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of indole-6-carboxylic acid (71 mg, 0.44 mmol), bromotris(pyrrolidino)phosphonium hexafluorophosphate (204 mg, 0.44 mmol) and diisopropylethylamine (0.153 mL, 0.88 mmol) in dry methylene chloride (5 mL) was stirred 10 min. 4-(tert-Butyldimethylsilyloxy)-N2-[1-(4-pyridyl)piperidin-4-yl]methoxycarbonyl-1,2-benzenediamine (100 mg, 0.22 mmol) and N,N-dimethylformamide (2 mL) were added and the resulting mixture stirred 64 h at ambient temperature. Saturated aqueous sodium hydrogen carbonate solution (4 mL) was added, and the resultant mixture stirred for 30 min. The mixture was partitioned between ethyl acetate and water, the organic solution separated, dried (anhydrous magnesium sulfate), filtered, and concentrated in vacuo. The residue was chromatographed (silica gel, methylene chloride, 9:1 methylene chloride/methanol, 9:1:0.1 methylene chloride/methanol/ammonium hydroxide) to yield 55 mg (44%) of the title compound.

Workup

  1. stirringthe resulting mixture stirred 64 h at ambient temperature
  2. customThe mixture was partitioned between ethyl acetate and water
  3. customthe organic solution separated
  4. dry with materialdried (anhydrous magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed (silica gel, methylene chloride, 9:1 methylene chloride/methanol, 9:1:0.1 methylene chloride/methanol/ammonium hydroxide)

Sources & evidence

ORD record
ord-7f69ee88358c4e42ad2c624a79fbfb50
Source dataset
uspto-grants-2002_12
Patent number
US06500851B2

Reaction notes

Loading…