Cesium carbonate → Methyl 2-(3-acetyl-5-(pyrimidin-2-ylmethoxy)-1H-indazol-1-yl)acetate

HRID 1527284Notes

Reaction equation

HRID 1527284 reaction equation
[C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([OH:13])[CH:11]=2)[N:6]([CH2:14][C:15]([O:17][CH3:18])=[O:16])[N:5]=1)(=[O:3])[CH3:2].Cl.Cl[CH2:21][C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N>[C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH2:21][C:22]3[N:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:11]=2)[N:6]([CH2:14][C:15]([O:17][CH3:18])=[O:16])[N:5]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 200256062-(Chloromethyl)pyrimidine hydrochlorideHCID 68283743Methyl 2-(3-acetyl-5-hydroxy-1H-indazol-1-yl)acetate

Product 1

HCID 68283900Methyl 2-(3-acetyl-5-(pyrimidin-2-ylmethoxy)-1H-indazol-1-yl)acetate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To methyl 2-(3-acetyl-5-hydroxy-1H-indazol-1-yl)acetate (1.80 g, 7.25 mmol) in CH3CN (75 mL) was added 2-(chloromethyl)pyrimidine hydrochloride salt (1.32 g, 7.98 mmol) and Cs2CO3 (5.91 g, 18.13 mmol). The reaction mixture was stirred at 70° C. for 2 h. The reaction mixture was filtered and washed with CH3CN. Solvent was evaporated and the crude mixture was purified by flash column chromatography on silica gel (gradient: c-hexane/EtOAc 1:1 to 1:3). TLC, Rf (c-hexane/EtOAc 1:3)=0.35; MS (LC/MS): 340.9 [M+H]+, 363.0 [M+Na]+; tR (HPLC conditions c): 3.64 min.

Workup

  1. filtrationThe reaction mixture was filtered
  2. washwashed with CH3CN
  3. customSolvent was evaporated
  4. customthe crude mixture was purified by flash column chromatography on silica gel (gradient: c-hexane/EtOAc 1:1 to 1:3)
  5. custom3.64 min.

Sources & evidence

ORD record
ord-ab6aefc048f14f3e942304f8498ba29c
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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