N,N-Dimethylglycine → HCID 59272925, compound

HRID 1406589Notes

Reaction equation

HRID 1406589 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[NH2:8][C@@H:9]([CH3:22])[C@@H:10]([C:12]1[CH:13]=[CH:14][C:15]2[CH2:20][O:19][CH2:18][O:17][C:16]=2[CH:21]=1)[OH:11].CN(C)CC(O)=O.I[C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[N:36]([C:40]1[CH:41]=[C:42]([CH:50]=[CH:51][CH:52]=1)[C:43]([O:45][CH2:46][CH:47]([CH3:49])[CH3:48])=[O:44])[N:35]=[CH:34]2>C(#N)CCC.[Cu]I>[NH2:8][C@@H:9]([CH3:22])[C@@H:10]([C:12]1[CH:13]=[CH:14][C:15]2[CH2:20][O:19][CH2:18][O:17][C:16]=2[CH:21]=1)[O:11][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[N:36]([C:40]1[CH:41]=[C:42]([CH:50]=[CH:51][CH:52]=1)[C:43]([O:45][CH2:46][CH:47]([CH3:48])[CH3:49])=[O:44])[N:35]=[CH:34]2

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 57432096HCID 57432096, compoundHCID 68577860HCID 68577860, compound

Product 1

HCID 59272925HCID 59272925, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8008ButyronitrileSolvent2×

Conditions

Temperature
110 °C

Procedure

A 250 mL one-neck round bottomed-flask with magnetic stirring and argon atmosphere was charged with cesium carbonate (30.3 g, 93.00 mmol), (1R,2S)-2-amino-1-(4H-benzo[d][1,3]dioxin-7-yl)propan-1-ol hydrochloride (I3) (7.37 g, 30.00 mmol), 2-(dimethylamino)acetic acid (1.547 g, 15.00 mmol), copper(I) iodide (1.428 g, 7.50 mmol) and butyronitrile (72 mL) and heated at 110° C. for 30 min. A solution of isobutyl 3-(5-iodo-1H-indazol-1-yl)benzoate (I1) (12.61 g, 30 mmol) in butyronitrile (12.00 mL) was generated by heating at 80° C. for 10 minutes. The solution was pumped to the above mixture within 3 minutes. The vessel was rinsed with further butyronitrile (6.00 mL) which also was added. The reaction mixture was sealed and stirred at 110° C. for 19 h. The reaction mixture was cooled and extracted between water and ethyl acetate (1 L). The organic phase was washed three times with water (3×500 mL), dried over magnesium sulfate and concentrated. The residue was purified by flash chromatography on silica using ethyl acetate:heptane 1:1 with 2% TEA followed by ethyl acetate:heptane 3:1 with 2% TEA and finally with ethyl acetate with 2% TEA. This gave the title compound (5.1 g, 34%).

Workup

  1. temperatureby heating at 80° C. for 10 minutes
  2. washThe vessel was rinsed with further butyronitrile (6.00 mL) which
  3. additionalso was added
  4. customThe reaction mixture was sealed
  5. stirringstirred at 110° C. for 19 h
  6. temperatureThe reaction mixture was cooled
  7. extractionextracted between water and ethyl acetate (1 L)
  8. washThe organic phase was washed three times with water (3×500 mL)
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography on silica

Sources & evidence

ORD record
ord-b3eec1df55a04e48859b2e394df8e325
Source dataset
uspto-grants-2014_12
Patent number
US08916600B2

Reaction notes

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