Acetonitrile → N-(3,5-Difluoro-benzyl)-N'-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-1-(1H-indol-3-ylmethyl)-2-oxo-ethyl]-2-methyl-malonamide

HRID 2223248Notes

Reaction equation

HRID 2223248 reaction equation
[NH2:1][CH:2]([CH2:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18][CH:17]=1)[C:3]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1)=[O:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:47][C:48]1[CH:49]=[C:50]([CH:60]=[C:61]([F:63])[CH:62]=1)[CH2:51][NH:52][C:53](=[O:59])[CH:54]([CH3:58])[C:55](O)=[O:56].CC#N>CN(C=O)C.C(O)(C(F)(F)F)=O>[F:47][C:48]1[CH:49]=[C:50]([CH:60]=[C:61]([F:63])[CH:62]=1)[CH2:51][NH:52][C:53](=[O:59])[CH:54]([CH3:58])[C:55]([NH:1][CH:2]([CH2:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18][CH:17]=1)[C:3]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1)=[O:4])=[O:56]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21091473N-(3,5-difluoro-benzyl)-2-methyl-malonamic acidHCID 69282442HCID 69282442, compound

Product 1

HCID 69280666N-(3,5-Difluoro-benzyl)-N'-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-1-(1H-indol-3-ylmethyl)-2-oxo-ethyl]-2-methyl-malonamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

2-Amino-1-(3,4-dihydro-1H-isoquinolin-2-yl)-3-(1H-indol-3-yl)-propan-1-one (57 mg, 0.18 mmol) was placed in a disposable polypropylene tube and dissolved in DMF (1 ml). TBTU (O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-tetrafluoroborate, 65 mg, 0.2 mmol) and N-(3,5-difluoro-benzyl)-2-methyl-malonamic acid (49 mg, 0.2 mmol) were added, and the mixture was shaken overnight at r.t. The title compound, MS: m/e=545.3 (M+H+), was isolated from the reaction mixture by automated, preparative HPLC (YMC CombiPrep C18 column 50×20 mm, solvent gradient 5-95% CH3CN in 0.1% TFA(aq) over 6.0 min, λ=230 nm, flow rate 40 ml/min).

Sources & evidence

ORD record
ord-b15a2d678a1148e48a3a1cd5275008a9
Source dataset
uspto-grants-2008_05
Patent number
US07375099B2

Reaction notes

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