Diisopropylethylamine → (3R)-N-Methyl-N-(1-pyridin-4-yl-piperidin-4-yl)-3-(3,3,3-trifluoropropanoyl-amino)-2,3-dihydro-1H-indene-5-carboxylic acid amide

HRID 1193420Notes

Reaction equation

HRID 1193420 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.[F:34][C:35]([F:41])([F:40])[CH2:36][C:37](O)=[O:38].[NH2:42][C@H:43]1[C:51]2[C:46](=[CH:47][CH:48]=[C:49]([C:52]([N:54]([CH3:67])[CH:55]3[CH2:60][CH2:59][N:58]([C:61]4[CH:66]=[CH:65][N:64]=[CH:63][CH:62]=4)[CH2:57][CH2:56]3)=[O:53])[CH:50]=2)[CH2:45][CH2:44]1>C1COCC1.ClCCl>[CH3:67][N:54]([CH:55]1[CH2:60][CH2:59][N:58]([C:61]2[CH:66]=[CH:65][N:64]=[CH:63][CH:62]=2)[CH2:57][CH2:56]1)[C:52]([C:49]1[CH:50]=[C:51]2[C:46](=[CH:47][CH:48]=1)[CH2:45][CH2:44][C@H:43]2[NH:42][C:37](=[O:38])[CH2:36][C:35]([F:41])([F:40])[F:34])=[O:53]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27779723,3,3-Trifluoropropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66798813(R)-3-Amino-N-methyl-N-(1-(pyridin-4-yl)piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide

Product 1

HCID 56941868(3R)-N-Methyl-N-(1-pyridin-4-yl-piperidin-4-yl)-3-(3,3,3-trifluoropropanoyl-amino)-2,3-dihydro-1H-indene-5-carboxylic acid amideYield 59%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

HATU (168 mg, 0.44 mmol, 1 eq) and DIPEA (200 μl, 1.1 mmol, 2.5 eq) were added to an ice-cooled solution of 3,3,3-trifluoropropionic acid (67.5 mg, 0.528 mmol, 1.2 eq) in THF (5 ml), and the mixture was stirred for 30 min. (R)-3-Amino-N-methyl-N-(1-(pyridin-4-yl)piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide (154 mg, 0.44 mmol, 1 eq) was dissolved in THF (2 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 (40 ml), sat. ammonium chloride solution (40 ml), water (40 ml) and sat. NaCl solution (40 ml), dried over sodium sulfate and concentrated under reduced pressure. After purification by column chromatography (silica gel, 5% MeOH in dichloromethane), the desired product was obtained in the form of a white solid. Yield: 59% (120 mg, 0.26 mmol).

Workup

  1. additionadded dropwise to the reaction solution
  2. washwashed with sat. sodium hydrogen carbonate solution (40 ml), sat. ammonium chloride solution (40 ml), water (40 ml) and sat. NaCl solution (40 ml)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customAfter purification by column chromatography (silica gel, 5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-21a41d485c0242dba20bff4ab0593b3a
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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