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

HRID 1052103Notes

Reaction equation

HRID 1052103 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 (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. The solvent was removed under reduced pressure and the crude residue was purified by flash column chromatography on silica gel (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 e): 3.64 min.

Workup

  1. filtrationThe reaction mixture was filtered
  2. washwashed with CH3CN
  3. customThe solvent was removed under reduced pressure
  4. customthe crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 1:1 to 1:3)
  5. custom3.64 min.

Sources & evidence

ORD record
ord-1870baa1c132469c99d134e7bce96348
Source dataset
uspto-grants-2016_07
Patent number
US09388199B2

Reaction notes

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