Diisopropylethylamine → HCID 59451493, compound

HRID 1874951Notes

Reaction equation

HRID 1874951 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][CH2:26][C:27]1[C:28]([F:44])=[C:29]([O:34][C:35]2[CH:36]=[C:37]([CH:40]=[C:41]([Cl:43])[CH:42]=2)[C:38]#[N:39])[C:30]([Cl:33])=[CH:31][CH:32]=1.[CH3:45][S:46][CH2:47][CH2:48][CH2:49][O:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][CH:59]=1)[NH:56][C:55]([C:60](O)=[O:61])=[CH:54]2.CCN(C(C)C)C(C)C>O.CCOC(C)=O.CN(C=O)C>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][NH:25][C:60]([C:55]2[NH:56][C:57]3[C:53]([CH:54]=2)=[CH:52][C:51]([O:50][CH2:49][CH2:48][CH2:47][S:46][CH3:45])=[CH:59][CH:58]=3)=[O:61])=[C:28]([F:44])[C:29]=1[O:34][C:35]1[CH:36]=[C:37]([C:38]#[N:39])[CH:40]=[C:41]([Cl:43])[CH:42]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 68480831HCID 68480831, compound

Product 1

HCID 59451493HCID 59451493, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (0.061 g, 0.161 mmol) was added as a solid to a DMF (1 mL) solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.050 g, 0.161 mmol), 5-{[3-(methylthio)propyl]oxy}-1H-indole-2-carboxylic acid (0.043 g, 0.161 mmol) and DIPEA (0.028 mL, 0.161 mmol). After stirring for 2 hours the reaction mixture was poured into EtOAc and water and the layers separated. The organic layer was dried over MgSO4, filtered and the solvent evaporated. The residue was dissolved in MeOH and purification was accomplished by reverse-phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.045 g, 50%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.45 (s, 1H), 8.96 (t, 1H), 7.80 (s, 1H), 7.43-7.54 (m, 3H), 7.37 (t, 1H), 7.28 (d, 1H), 7.01-7.10 (m, 2H), 6.82 (dd, 1H), 4.54 (d, 2H), 4.00 (t, 2H), 2.61 (t, 2H), 2.04 (s, 3H), 1.89-2.01 (m, 2H). LCMS: m/z 558.1 (M+1).

Workup

  1. customthe layers separated
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customthe solvent evaporated
  5. dissolutionThe residue was dissolved in MeOH
  6. custompurification

Sources & evidence

ORD record
ord-58e8a64f0e4f4709a1ddb1dca2dfefe6
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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