Sodium Hydroxide → HCID 123569342, compound

HRID 921091Notes

Reaction equation

HRID 921091 reaction equation
[CH2:1]([O:4][CH:5]([C:10]1[N:11]=[N:12][N:13]([CH2:15][C:16]2[CH:47]=[C:19]3[N:20]=[C:21]([CH3:46])[C:22]([C@H:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[C:36]([O:38]CC)=[O:37])=[C:23]([N:24]4[CH2:29][CH2:28][C:27]([O:31][CH2:32][CH:33]=C)([CH3:30])[CH2:26][CH2:25]4)[N:18]3[N:17]=2)[CH:14]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH:2]=C.[OH-].[Na+]>ClCCCl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1.CO>[C:42]([O:41][C@@H:35]([C:22]1[C:21]([CH3:46])=[N:20][C:19]2=[CH:47][C:16]3=[N:17][N:18]2[C:23]=1[N:24]1[CH2:29][CH2:28][C:27]([CH3:30])([O:31][CH2:32][CH:33]=[CH:2][CH2:1][O:4][CH:5]([CH2:6][CH:7]([CH3:8])[CH3:9])[C:10]2[N:11]=[N:12][N:13]([CH:14]=2)[CH2:15]3)[CH2:26][CH2:25]1)[C:36]([OH:38])=[O:37])([CH3:45])([CH3:43])[CH3:44]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 118318756HCID 118318756, compound

Product 1

HCID 123569342HCID 123569342, compoundYield 119%

Reagents, catalysts & solvents 3

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumCatalystHCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

To a stirred solution of (2S)-ethyl 2-(2-((4-(1-(allyloxy)-3-methylbutyl)-1H-1,2,3-triazol-1-yl)methyl)-7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.080 g, 0.123 mmol) in 1,2-dichloroethane (30 mL) was added Hoveyda-Grubbs catalyst 2nd generation (3.85 mg, 6.14 μmol) at 70° C. After 2 h at 75° C., the reaction mixture was filtered through a plug of silica gel (washed with 10 mL of EtOAC), concentrated and used in the next step without purification. A solution of above crude ester and NaOH (0.491 ml, 0.491 mmol) in MeOH (4 mL) was refluxed for 2 h. Then, cooled and purified by prep-HPLC to afford mixture of diastereomers (0.087 g, 0.146 mmol, 119% yield) as white solid. LCMS (M+H)=596.7.

Workup

  1. filtrationthe reaction mixture was filtered through a plug of silica gel (washed with 10 mL of EtOAC)
  2. concentrationconcentrated
  3. customused in the next step without purification
  4. temperatureThen, cooled
  5. custompurified by prep-HPLC
  6. customto afford
  7. additionmixture of diastereomers (0.087 g, 0.146 mmol, 119% yield) as white solid

Sources & evidence

ORD record
ord-91c7e502083b4868a11c555cab0aac50
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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