3,4-Dimethylpentanoic acid → (3R)-Methyl 3-(3,4-dimethylpentanamido)-2,3-dihydro-1H-indene-5-carboxylate

HRID 1193278Notes

Reaction equation

HRID 1193278 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][CH:26]([CH:31]([CH3:33])[CH3:32])[CH2:27][C:28](O)=[O:29].Cl.[CH3:35][O:36][C:37]([C:39]1[CH:40]=[C:41]2[C:45](=[CH:46][CH:47]=1)[CH2:44][CH2:43][C@H:42]2[NH2:48])=[O:38]>C1COCC1.C(OCC)(=O)C>[CH3:25][CH:26]([CH:31]([CH3:33])[CH3:32])[CH2:27][C:28]([NH:48][C@H:42]1[C:41]2[C:45](=[CH:46][CH:47]=[C:39]([C:37]([O:36][CH3:35])=[O:38])[CH:40]=2)[CH2:44][CH2:43]1)=[O:29]

Participants

6

Reactant 3

HCID 2261133,4-Dimethylpentanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66700566(R)-methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate hydrochloride

Product 1

HCID 66805314(3R)-Methyl 3-(3,4-dimethylpentanamido)-2,3-dihydro-1H-indene-5-carboxylateYield 87%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (0.872 g, 2.3 mmol, 1 eq) and TEA (0.647 ml, 4.6 mmol, 2 eq) were added to an ice-cooled solution of 3,4-dimethylpentanoic acid (300 mg, 2.3 mmol, 1 eq) in THF (26 ml), and stirring was carried out for 15 min. (3R)-3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-01) (0.786 g, 3.5 mmol, 1.5 eq) was added to the reaction solution, and the mixture was then stirred overnight at RT. The reaction solution was diluted with ethyl acetate, washed with sat. sodium hydrogen carbonate solution and sat. NaCl solution, dried over magnesium sulfate and concentrated under reduced pressure. After purification by column chromatography (silica gel, cyclohexane:ethyl acetate 2:1), the desired product was obtained. Yield: 87% (0.61 g)

Workup

  1. stirringthe mixture was then stirred overnight at RT
  2. washwashed with sat. sodium hydrogen carbonate solution and sat. NaCl solution
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customAfter purification by column chromatography (silica gel, cyclohexane:ethyl acetate 2:1)

Sources & evidence

ORD record
ord-40794eebb6bb4d01b8a30847d6d471bb
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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