L-Proline → HCID 86724435, compound

HRID 2369535Notes

Reaction equation

HRID 2369535 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][C@@H:8]([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:9][O:10][C:11]1[C:12](Br)=[CH:13][C:14]2[C:24]3[C:19](=[CH:20][N:21]=[CH:22][CH:23]=3)[CH:18]([CH3:25])[O:17][C:15]=2[CH:16]=1)([CH3:4])([CH3:3])[CH3:2].[NH:32]1CCC[C@H:33]1C(O)=O.[Cu]C#N>CN(C=O)C>[C:1]([O:5][C:6](=[O:31])[NH:7][C@@H:8]([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:9][O:10][C:11]1[C:12]([C:33]#[N:32])=[CH:13][C:14]2[C:24]3[C:19](=[CH:20][N:21]=[CH:22][CH:23]=3)[CH:18]([CH3:25])[O:17][C:15]=2[CH:16]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 145742L-ProlineHCID 86724436HCID 86724436, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 86724435HCID 86724435, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of tert-butyl((2S)-1-((9-bromo-5-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (100 mg, 0.203 mmol) (prepared as described in Example 21, Part A) and L-proline (23.43 mg, 0.203 mmol) in DMF (2 mL) was added copper(I) cyanide (36.5 mg, 0.407 mmol). Argon gas was bubbled through the stirred suspension for 5 min. The reaction mixture was stirred under argon atmosphere at 120° C. for 12 h. The mixture was then cooled to room temperature and diluted with ethyl acetate (10 mL) and filtered through celite. The filtrate was washed with water (10 mL) and brine (10 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure to afford crude material which was purified via silica gel chromatography (pet ether: ethyl acetate mobile phase) to afford tert-butyl((2S)-1-((9-cyano-5-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (15 mg, 0.034 mmol, 17% yield). LCMS (ESI) m/e 438.2 [(M+H)+, calcd for C25H32N3O4438.2] LC/MS retention time (method D): tR=1.81 min.

Workup

  1. customprepared
  2. customArgon gas was bubbled through the stirred suspension for 5 min
  3. temperatureThe mixture was then cooled to room temperature
  4. additiondiluted with ethyl acetate (10 mL)
  5. filtrationfiltered through celite
  6. washThe filtrate was washed with water (10 mL) and brine (10 mL)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customto afford crude material which
  10. customwas purified via silica gel chromatography (pet ether: ethyl acetate mobile phase)

Sources & evidence

ORD record
ord-f376a275cfba497699c6bec400bded35
Source dataset
uspto-grants-2014_04
Patent number
US08703953B2

Reaction notes

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