Diisopropylethylamine → 5-(methyloxy)-1-(1-methyl-L-prolyl)-6-nitro-2,3-dihydro-1H-indole

HRID 1014284Notes

Reaction equation

HRID 1014284 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[NH:8][CH2:7][CH2:6]2.[CH3:15][N:16]1[CH2:23][CH2:22][CH2:21][C@H:17]1[C:18](O)=[O:19].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O.C(OCC)(=O)C.C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[N:8]([C:18](=[O:19])[C@@H:17]1[CH2:21][CH2:22][CH2:23][N:16]1[CH3:15])[CH2:7][CH2:6]2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 643474N-Methyl-L-prolineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594416565-methoxy-6-nitro-2,3-dihydro-1H-indole

Product 1

HCID 673158805-(methyloxy)-1-(1-methyl-L-prolyl)-6-nitro-2,3-dihydro-1H-indoleYield 95.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

A solution of 5-(methyloxy)-6-nitro-2,3-dihydro-1H-indole (2.7 g, 11.71 mmol), 1-methyl-L-proline (Acros, 1.739 g, 13.46 mmol), HATU (5.79 g, 15.22 mmol), and DIPEA (6.13 mL, 35.1 mmol) in N,N-Dimethylformamide (DMF) (25 mL) was stirred at room temperature overnight. The next morning the solution had completely solidified. The solids were diluted with ethyl acetate/THF and washed with saturated sodium bicarbonate until all solids had dissolved. The organic layer was dried over sodium sulfate, filtered, concentrated onto celite, and purified by column chromatography to afford 5-(methyloxy)-1-(1-methyl-L-prolyl)-6-nitro-2,3-dihydro-1H-indole (3.4 g, 95% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.51 (s, 1 H), 7.35 (s, 1 H), 4.20-4.31 (m, 1 H), 4.10-4.20 (m, 1 H), 3.88 (s, 3 H), 3.56-3.70 (m, 1 H), 3.25 (t, J=8.43 Hz, 2 H), 3.15-3.21 (m, 1 H), 2.52-.64 (m, 1H), 2.45 (s, 3 H), 2.21-2.35 (m, 1 H), 1.75-1.93 (m, 3 H).

Workup

  1. washwashed with saturated sodium bicarbonate until all solids
  2. dissolutionhad dissolved
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated onto celite
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-75e4a29d7e704436bb9e0c616f0a76ef
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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