Sodium hydride → (S)-1-(tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acid (3-[1,1-dimethyl-2-(tetrahydro-pyran-2-yloxy)-ethyl]-isoxazol-5-yl)-amide

HRID 469751Notes

Reaction equation

HRID 469751 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH2:11][CH2:10][CH2:9][C@H:8]2[C:12]([OH:14])=O)[CH2:3][CH2:2]1.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)C.[CH3:47][C:48]([C:58]1[CH:62]=[C:61]([NH2:63])[O:60][N:59]=1)([CH3:57])[CH2:49][O:50][CH:51]1[CH2:56][CH2:55][CH2:54][CH2:53][O:52]1.[H-].[Na+]>CN(C)C=O>[CH3:57][C:48]([C:58]1[CH:62]=[C:61]([NH:63][C:12]([C@@H:8]2[CH2:9][CH2:10][CH2:11][N:7]2[CH:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)=[O:14])[O:60][N:59]=1)([CH3:47])[CH2:49][O:50][CH:51]1[CH2:56][CH2:55][CH2:54][CH2:53][O:52]1

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 521913N,N-Diethyl-2-propanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 51980116(S)-1-(Tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acidHCID 592532173-[1,1-Dimethyl-2-(tetrahydropyran-2-yloxy)-ethyl]-isoxazol-5-ylamine

Product 1

HCID 67953847(S)-1-(tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acid (3-[1,1-dimethyl-2-(tetrahydro-pyran-2-yloxy)-ethyl]-isoxazol-5-yl)-amideYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

(S)-1-(Tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acid (0.2 g; 1.004 mmol) is dissolved in 5 mL of dimethyl formamide and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium PF6 (0.573 g, 1.506 mmol) and diethylisopropyl amine (0.626 mL, 3.514 mmol) are added. The mixture is stirred at room temperature for 30 minutes. 3-[1,1-dimethyl-2-(tetrahydro-pyran-2-yloxy)-ethyl]isoxazole-5-yl amine (0.241 g, 1.004 mmol) is dissolved in 5 mL of dimethylformamide and sodium hydride (60% in mineral oil, 0.1 g, 2.510 mmol) is added at 0° C. The above solution is added and the mixture warmed to room temperature and stirred for 1 h. The reaction is quenched with water and methanol and concentrated under reduced pressure. The crude mixture is purified by flash chromatraphy (SiO2) to afford 0.075 g of title compound as an oil. 18% yield, ESI m/z 422=MH+.

Workup

  1. additionThe above solution is added
  2. temperaturethe mixture warmed to room temperature
  3. stirringstirred for 1 h
  4. customThe reaction is quenched with water and methanol
  5. concentrationconcentrated under reduced pressure
  6. customThe crude mixture is purified by flash chromatraphy (SiO2)

Sources & evidence

ORD record
ord-d29dfb50701c4d34ae0cc9ada55e09ee
Source dataset
uspto-grants-2014_01
Patent number
US08629157B2

Reaction notes

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