Diisopropylethylamine → (R)-tert-Butyl 6-(methyl(1-(pyridin-4-yl)piperidin-4-yl)carbamoyl)-2,3-dihydro-1H-inden-1-ylcarbamate

HRID 1193418Notes

Reaction equation

HRID 1193418 reaction equation
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.[C:34]([O:38][C:39]([NH:41][C@H:42]1[C:50]2[C:45](=[CH:46][CH:47]=[C:48]([C:51]([OH:53])=O)[CH:49]=2)[CH2:44][CH2:43]1)=[O:40])([CH3:37])([CH3:36])[CH3:35].[CH3:54][NH:55][CH:56]1[CH2:61][CH2:60][N:59]([C:62]2[CH:67]=[CH:66][N:65]=[CH:64][CH:63]=2)[CH2:58][CH2:57]1>C1COCC1.ClCCl>[CH3:54][N:55]([CH:56]1[CH2:57][CH2:58][N:59]([C:62]2[CH:63]=[CH:64][N:65]=[CH:66][CH:67]=2)[CH2:60][CH2:61]1)[C:51]([C:48]1[CH:49]=[C:50]2[C:45]([CH2:44][CH2:43][C@H:42]2[NH:41][C:39](=[O:40])[O:38][C:34]([CH3:35])([CH3:36])[CH3:37])=[CH:46][CH:47]=1)=[O:53]

Participants

7

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 17852018N-methyl-1-(pyridin-4-yl)piperidin-4-amineHCID 66798654(3R)-3-{[(tert-butoxy)carbonyl]amino}-2,3-dihydro-1H-indene-5-carboxylic acid

Product 1

HCID 66798862(R)-tert-Butyl 6-(methyl(1-(pyridin-4-yl)piperidin-4-yl)carbamoyl)-2,3-dihydro-1H-inden-1-ylcarbamateYield 64%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

HATU (0.795 g, 2.09 mmol, 1 eq) and DIPEA (350 μA 2.04 mmol, 2.5 eq) were added to an ice-cooled solution of (R)-3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid (368 mg, 2.09 mmol, 1 eq) in THF (5 ml), and stirring was carried out for 30 min. N-Methyl-1-(pyridin-4-yl)piperidin-4-amine (AMN-06) (400 mg, 2.09 mmol, 1 eq) was dissolved in THF (5 ml) and added dropwise to the reaction solution, and stirring was carried out for 16 h at RT. The reaction solution was diluted with dichloromethane (100 ml), washed with sat. sodium hydrogen carbonate solution (50 ml), sat. ammonium chloride solution (50 ml), water (50 ml) and sat. NaCl solution (50 ml), dried over sodium sulfate and concentrated under reduced pressure. After purification by column chromatography (silica gel, 0.5% MeOH in dichloromethane), the desired product was obtained in the form of a yellowish solid. Yield: 64% (600 mg, 1.33 mmol).

Workup

  1. additionadded dropwise to the reaction solution
  2. stirringstirring
  3. waitwas carried out for 16 h at RT
  4. washwashed with sat. sodium hydrogen carbonate solution (50 ml), sat. ammonium chloride solution (50 ml), water (50 ml) and sat. NaCl solution (50 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customAfter purification by column chromatography (silica gel, 0.5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-ec2e0bf5e8de43749aca068e08f12ef6
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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