Diisopropylethylamine → 1,1-dimethylethyl (2-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-indol-6-yl)carbamate

HRID 1874834Notes

Reaction equation

HRID 1874834 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][C:46]([O:49][C:50]([NH:52][C:53]1[CH:61]=[C:60]2[C:56]([CH:57]=[C:58]([C:62](O)=[O:63])[NH:59]2)=[CH:55][CH:54]=1)=[O:51])([CH3:48])[CH3:47].CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.O>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][NH:25][C:62]([C:58]2[NH:59][C:60]3[C:56]([CH:57]=2)=[CH:55][CH:54]=[C:53]([NH:52][C:50](=[O:51])[O:49][C:46]([CH3:47])([CH3:45])[CH3:48])[CH:61]=3)=[O:63])=[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 594515396-(Tert-butoxycarbonylamino)-1h-indole-2-carboxylic acid

Product 1

HCID 594515231,1-dimethylethyl (2-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-indol-6-yl)carbamateYield 54%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (0.104 g, 0.272 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.056 g, 0.182 mmol), 6-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1H-indole-2-carboxylic acid (0.050 g, 0.182 mmol) and DIPEA (0.048 mL, 0.272 mmol) in DMF (1.5 mL). The mixture was stirred at RT for 1.5 h. The reaction mixture was diluted with ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate, and the solvent was evaporated. The residue was purified by column chromatography (hexane/EtOAc) to give the title compound (0.056 g, 48%) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ ppm 9.74 (s, 1H), 7.78 (s, 1H), 7.44 (d, 1H), 7.27-7.37 (m, 2H), 7.21 (dd, 1H), 7.08-7.13 (m, 1H), 6.98 (d, 1H), 6.74-6.86 (m, 3H), 6.63 (s, 1H), 4.66 (d, 2H), 1.50 (s, 9H). MS: m/z 569 (M+1).

Workup

  1. washThe organic layer was washed with water and brine
  2. dry with materialdried over sodium sulfate
  3. customthe solvent was evaporated
  4. customThe residue was purified by column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-25cf22fe2140497894943debe9721b30
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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