Diisopropylethylamine → 5-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid [(R)-3-oxo-2-(tetrahydro-pyran-4-yl)-isoxazolidin-4-yl]-amide

HRID 38040Notes

Reaction equation

HRID 38040 reaction equation
N1C2C(=NC=CC=2)N([N:10]2[C:14](/[CH:15]=[C:16]3\[C:17](=[O:26])[NH:18][C:19]4[C:24]\3=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)=[C:13]([CH3:27])[C:12]([C:28]([O-:30])=O)=[C:11]2[CH3:31])N=1.[NH2:32][C@@H:33]1[CH2:37][O:36][N:35]([CH:38]2[CH2:43][CH2:42][O:41][CH2:40][CH2:39]2)[C:34]1=[O:44].CCN(C(C)C)C(C)C>CN(C=O)C>[O:44]=[C:34]1[C@H:33]([NH:32][C:28]([C:12]2[C:13]([CH3:27])=[C:14](/[CH:15]=[C:16]3\[C:17](=[O:26])[NH:18][C:19]4[C:24]\3=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[NH:10][C:11]=2[CH3:31])=[O:30])[CH2:37][O:36][N:35]1[CH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 57440953(r)-4-Amino-2-(tetrahydro-pyran-4-yl)-isoxazolidin-3-oneHCID 131727992(Z)-3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylate

Product 1

HCID 592159955-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid [(R)-3-oxo-2-(tetrahydro-pyran-4-yl)-isoxazolidin-4-yl]-amideYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of A4 (84 mg, 2 mmol) in 10 mL of DMF, were added the crude 48c from last step and DIEA (2 mL), the reaction mixture was stirred at room temperature overnight. LC/MS was applied to determine completion of the reaction. The reaction mixture was evaporated under reduced pressure and the residue was triturated with 5% diethylamine/methanol (25 mL). The solid was collected by filtration and washed with methanol, dried under vacuum to provide the title compound (58 mg, 62%) as orange solid. 1H NMR (300 MHz, DMSO-d6): δ=13.73 (s, 1H), 10.94 (s, 1H), 8.12-8.15 (d, 1H), 7.73-7.80 (m, 2H), 6.82-6.87 (m, 2H), 5.02-5.05 (q, 1H), 4.58-4.64 (t, 1H), 3.86-4.14 (m, 4H), 3.38-3.44 (m, 2H), 2.42-2.50 (ds, 6H), 1.65-1.88 (m, 4H). LC/MS: 469.0 [M+H]+.

Workup

  1. customcompletion of the reaction
  2. customThe reaction mixture was evaporated under reduced pressure
  3. customthe residue was triturated with 5% diethylamine/methanol (25 mL)
  4. filtrationThe solid was collected by filtration
  5. washwashed with methanol
  6. customdried under vacuum

Sources & evidence

ORD record
ord-b3e2351746ab45e592981af1126078f5
Source dataset
uspto-grants-2013_09
Patent number
US08524709B2

Reaction notes

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