HCID 118236081, compound → HCID 118236083, compound

HRID 1481302Notes

Reaction equation

HRID 1481302 reaction equation
[CH3:1][O:2][C:3]([NH:5][C:6]1[CH:23]=[C:22]2[C:9]([C:10]3[CH:11]=[CH:12][N:13]=[C:14]([CH:34]=3)[C@@H:15]([NH:26]C(=O)OC(C)(C)C)[CH2:16][CH2:17][CH2:18][C:19](=[O:25])[C:20](=[O:24])[NH:21]2)=[CH:8][CH:7]=1)=[O:4].[CH3:35][Mg]Br>C1COCC1>[NH2:26][C@@H:15]1[C:14]2[CH:34]=[C:10]([CH:11]=[CH:12][N:13]=2)[C:9]2[C:22](=[CH:23][C:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])=[CH:7][CH:8]=2)[NH:21][C:20](=[O:24])[C:19]([OH:25])([CH3:35])[CH2:18][CH2:17][CH2:16]1

Participants

4

Reactant 2

HCID 118236081HCID 118236081, compoundHCID 178418573HCID 178418573, compound3×

Product 1

HCID 118236083HCID 118236083, compoundYield 29.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 123C (345 mg, 0.736 mmol) in THF (7 mL) was cooled to 0° C. and treated with methylmagnesium bromide (0.245 mL, 0.736 mmol), then stirred at rt for 1 hr. The reaction was cooled to 0° C. again and treated with methylmagnesium bromide (0.491 mL, 1.473 mmol), then stirred at rt for 1 hr. LCMS still showed starting material. The reaction was cooled to 0° C., treated with methylmagnesium bromide (0.491 mL, 1.473 mmol), then stirred at rt overnight. The reaction was quenched with sat. NH4Cl, then diluted with EtOAc and water. The aqueous layer was extracted with EtOAc (3×), and the organic extracts were dried (Na2SO4), filtered, and concentrated. The residue was purified by prep HPLC. The pure material was dissolved in DCM and treated with TFA, then stirred at rt for 2 hrs. The solvent was removed in vacuo and 123D (135 mg, 0.220 mmol, 29.9% yield) was obtained as a yellow solid. The material was used in future steps without purification. MS (ESI) m/z: 385.1 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to 0° C. again
  2. stirringstirred at rt for 1 hr
  3. temperatureThe reaction was cooled to 0° C.
  4. stirringstirred at rt overnight
  5. customThe reaction was quenched with sat. NH4Cl
  6. additiondiluted with EtOAc and water
  7. extractionThe aqueous layer was extracted with EtOAc (3×)
  8. dry with materialthe organic extracts were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by prep HPLC
  12. dissolutionThe pure material was dissolved in DCM
  13. additiontreated with TFA
  14. stirringstirred at rt for 2 hrs
  15. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-8078c2e8f0174c84aed1a002e007f7e4
Source dataset
uspto-grants-2016_08
Patent number
US09409908B2

Reaction notes

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