Diisopropylethylamine → HCID 178437629, compound

HRID 1875114Notes

Reaction equation

HRID 1875114 reaction equation
C[N:2](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.C(NC1C=[C:51]2[C:55](=[CH:56][CH:57]=1)[NH:54][C:53]([C:58]([OH:60])=O)=[CH:52]2)(=O)C.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][NH:25][C:58]([C:53]2[NH:54][C:55]([CH2:56][CH3:57])=[N:2][C:52]=2[CH3:51])=[O:60])=[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

6

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 107751705-acetamido-1H-indole-2-carboxylic AcidHCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 178437629HCID 178437629, compoundYield 6.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (114 mg, 0.3 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (62 mg, 0.2 mmol), 5-(acetylamino)-1H-indole-2-carboxylic acid (31 mg, 0.2 mmol) and diisopropylethylamine (52 uL, 0.3 mmol) in DMF (1 mL). The reaction mixture was stirred at RT overnight and was extracted with ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate and concentrated. The residue was purified by column chromatography (0-5% 2M NH3 solution of MeOH in DCM) and preparative TLC (5% 2M NH3 solution of MeOH in DCM) to afford the title compound (5.5 mg) as a white solid. 1H NMR (400 MHz, CDCl3-d): δ ppm 8.85 (s, 1H) 7.54 (s, 1H) 7.31-7.38 (m, 2H) 7.20-7.27 (m, 1H) 7.14 (s, 1H) 7.01 (s, 1H) 4.62 (d, J=6.41 Hz, 2H) 2.67 (q, J=7.69 Hz, 2H) 2.55 (s, 3H) 1.29 (t, J=7.69 Hz, 3H). LCMS: m/z 447 (M+1).

Workup

  1. extractionwas extracted with ethyl acetate and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (0-5% 2M NH3 solution of MeOH in DCM) and preparative TLC (5% 2M NH3 solution of MeOH in DCM)

Sources & evidence

ORD record
ord-5e6badd7a9914ae4b792be1952e181cd
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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