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

HRID 1875036Notes

Reaction equation

HRID 1875036 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.[Cl: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>[Cl: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 684853213-chloro-5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1H-indole-2-carboxylic acid

Product 1

HCID 866449121,1-dimethylethyl (3-chloro-2-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-indol-5-yl)carbamateYield 26.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.119 g, 0.314 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.055 g, 0.209 mmol), 3-chloro-5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1H-indole-2-carboxylic acid (0.065 g, 0.209 mmol) and diisopropylethylamine (0.055 mL, 0.314 mmol) in DMF (1 mL). The mixture was stirred at room temperature overnight. 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 (0.033 g, 26%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.75 (s, 1H), 9.28 (br. s., 1H), 8.44 (t, 1H), 7.78 (br. s., 2H), 7.48 (d, 2H), 7.35-7.45 (m, 2H), 7.26-7.32 (m, 1H), 7.19-7.26 (m, 1H), 4.58 (d, 2H), 1.42 (s, 9H). ES MS: m/z 601 (M−1).

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-649640a5800a43838ab249c62344cb01
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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