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

HRID 1875040Notes

Reaction equation

HRID 1875040 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.[Br:45][C:46]1[C:54]2[C:49](=[CH:50][CH:51]=[C:52]([NH:55][C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[CH:53]=2)[NH:48][C:47]=1[C:63](O)=[O:64].C(N(C(C)C)CC)(C)C>CN(C=O)C>[Br:45][C:46]1[C:54]2[C:49](=[CH:50][CH:51]=[C:52]([NH:55][C:56](=[O:57])[O:58][C:59]([CH3:60])([CH3:61])[CH3:62])[CH:53]=2)[NH:48][C:47]=1[C:63]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([O:34][C:35]2[CH:36]=[C:37]([C:38]#[N:39])[CH:40]=[C:41]([Cl:43])[CH:42]=2)[C:28]=1[F:44])=[O:64]

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 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 684865673-bromo-5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1H-indole-2-carboxylic acid

Product 1

HCID 866449141,1-dimethylethyl (3-bromo-2-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-indol-5-yl)carbamateYield 32.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.231 g, 0.608 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.126 g, 0.405 mmol), 3-bromo-5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1H-indole-2-carboxylic acid (0.144 g, 0.405 mmol) and diisopropylethylamine (0.106 mL, 0.608 mmol) in DMF (3 mL). The mixture was stirred at room temperature for 1 hr. The reaction mixture was extracted with ethyl acetate and water. The organic layer was washed with water, dried over sodium sulfate and concentrated. The residue was triturated with methanol to give the title compound (0.086 g, 31%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.84 (br. s., 1H), 9.27 (br. s., 1H), 8.45 (br. s., 1H), 7.66-7.84 (m, 2H), 7.38-7.56 (m, 4H), 7.17-7.34 (m, 2H), 4.57 (d, 2H), 1.14-1.62 (m, 9H).

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate and water
  2. washThe organic layer was washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was triturated with methanol

Sources & evidence

ORD record
ord-9057540f288046119a5a643780cb1151
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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