Diisopropylethylamine → HCID 46190327, compound

HRID 2360519Notes

Reaction equation

HRID 2360519 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]([OH:10])=O)[CH2:4][CH2:3]1.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.F[B-](F)(F)F.C(N(CC)C(C)C)(C)C.[C:42]([C:46]1[CH:47]=[C:48]([NH:74][S:75]([CH3:78])(=[O:77])=[O:76])[C:49]([O:72][CH3:73])=[C:50]([NH:52][C:53]([C:55]2[N:56]([CH3:71])[C:57]3[C:62]([CH:63]=2)=[CH:61][CH:60]=[CH:59][C:58]=3[CH2:64][N:65]2[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]2)=[O:54])[CH:51]=1)([CH3:45])([CH3:44])[CH3:43]>CN(C)C=O.C(OCC)(=O)C.O>[C:42]([C:46]1[CH:47]=[C:48]([NH:74][S:75]([CH3:78])(=[O:77])=[O:76])[C:49]([O:72][CH3:73])=[C:50]([NH:52][C:53]([C:55]2[N:56]([CH3:71])[C:57]3[C:62]([CH:63]=2)=[CH:61][CH:60]=[CH:59][C:58]=3[CH2:64][N:65]2[CH2:66][CH2:67][N:68]([C:8]([CH:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]3)=[O:10])[CH2:69][CH2:70]2)=[O:54])[CH:51]=1)([CH3:45])([CH3:43])[CH3:44]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27369391-Methylpiperidine-4-carboxylic acidHCID 59856627HCID 59856627, compound

Product 1

HCID 46190327HCID 46190327, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

61 mg 1-methyl-piperidine-4-carboxylic acid are dissolved in 1 ml N,N-dimethylformamide and combined with 137 mg O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-tetrafluoroborate (TBTU) and 138 μl N,N-diisopropyl-ethylamine (DIEA). The mixture is stirred for 20 minutes, then 150 mg 1-methyl-7-piperazin-1-ylmethyl-1H-indole-2-carboxylic acid(5-tert-butyl-3-methanesulphonylamino-2-methoxy-phenyl)-amide are added and the mixture is stirred for 12 hours. Then it is divided between water and ethyl acetate and the aqueous phase is extracted twice with ethyl acetate. The combined organic phases are washed with saturated aqueous sodium chloride solution and dried on magnesium sulphate. Then the solvents are eliminated in vacuo and the residue is chromatographed on silica gel with dichloromethane/(methanol/ammonia 9:1) 99:1 to 90:10.

Workup

  1. stirringthe mixture is stirred for 12 hours
  2. extractionthe aqueous phase is extracted twice with ethyl acetate
  3. washThe combined organic phases are washed with saturated aqueous sodium chloride solution
  4. customdried on magnesium sulphate
  5. customthe residue is chromatographed on silica gel with dichloromethane/(methanol/ammonia 9:1) 99:1 to 90:10

Sources & evidence

ORD record
ord-69b0d4120b9649ce9647b2d2333a6467
Source dataset
uspto-grants-2014_04
Patent number
US08686022B2

Reaction notes

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