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

HRID 1874817Notes

Reaction equation

HRID 1874817 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:54]=[C:55]2[C:59](=[CH:60][CH:61]=1)[NH:58][C:57]([C:62](O)=[O:63])=[CH:56]2)=[O:51])([CH3:48])[CH3:47].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.O>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][NH:25][C:62]([C:57]2[NH:58][C:59]3[C:55]([CH:56]=2)=[CH:54][C:53]([NH:52][C:50](=[O:51])[O:49][C:46]([CH3:47])([CH3:45])[CH3:48])=[CH:61][CH:60]=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 158871475-(((tert-butoxy)carbonyl)amino)-1H-indole-2-carboxylic acidHCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 594514661,1-dimethylethyl (2-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-indol-5-yl)carbamateYield 60%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (0.064 g, 0.168 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.035 g, 0.112 mmol), 5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1H-indole-2-carboxylic acid (0.032 g, 0.116 mmol), and DIPEA (0.030 ml, 0.168 mmol) in DMF (1 mL). The mixture was stirred at RT for 1.5 h. Water and EtOAc were added. The organic layer was separated and washed with water and brine, dried over sodium sulfate, and concentrated to give the title compound (0.038 g, 60%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ ppm 9.67 (s, 1H), 7.75 (s, 1H), 7.17-7.37 (m, 4H), 7.14 (t, 1H), 7.08 (dd, 1H), 6.94-7.02 (m, 2H), 6.80 (m, 1H), 6.60 (s, 1H), 4.69 (d, 2H), 1.52 (m, 9H). MS: m/z 569 (M).

Workup

  1. customThe organic layer was separated
  2. washwashed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-c43f09bab756402ead9ea1f751d3a151
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…