Cesium carbonate → HCID 25054013, compound

HRID 2387496Notes

Reaction equation

HRID 2387496 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([CH2:24][CH2:25]Cl)[N:19]=[CH:18]3)[C:11](=[O:27])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[OH:34][CH2:35][C@H:36]1[CH2:40][CH2:39][CH2:38][NH:37]1>CN(C=O)C.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([CH2:24][CH2:25][N:37]2[CH2:38][CH2:39][CH2:40][C@@H:36]2[CH2:35][OH:34])[N:19]=[CH:18]3)[C:11](=[O:27])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2724541Prolinol, (R)-HCID 59293392HCID 59293392, compound

Product 1

HCID 25054013HCID 25054013, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-(benzyloxy)-1-(1-(2-chloroethyl)-1H-indazol-5-yl)pyridin-2(1H)-one (0.15 g, 0.40 mmol) in DMF (2.1 mL) was added Cs2CO3 (0.64 g, 2.0 mmol) and (R)-2-hydroxymethylpyrrolidine (0.78 mL, 7.9 mmol). The reaction mixture was heated at 90° C. for 3 h. The reaction mixture was cooled and diluted with H2O (25 mL) and was extracted with EtOAc (3×20 mL) The organic extracts were washed with brine (2×20 mL), dried (Na2SO4), filtered and concentrated. Purification by flash chromatography (silica gel, Hexanes/EtOAc/9:1 MeOH/NH4OH, 1:1:0 to 9:9:2) followed by preparative HPLC (Phenomenex Luna C18 (2), 250.0×21.2 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA) gave the title compound (30 mg, 17%) as a clear film. 1H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.67 (s, 1H), 7.49-7.46 (m, 1H), 7.42-7.36 (m, 6H), 7.30-7.26 (m, 1H), 6.09-6.08 (m, 2H), 5.06 (s, 2H), 4.50-4.49 (m, 2H), 3.47-3.45 (m, 1H), 3.39-3.37 (m, 1H), 3.28-3.19 (m, 2H), 2.88-2.86 (m, 1H) 2.69 (br s, 1H), 2.60-2.45 (br s, 1H), 2.39-2.38 (m, 1H), 1.86-1.70 (m, 4H); ESI MS m/z 445 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionwas extracted with EtOAc (3×20 mL) The organic extracts
  3. washwere washed with brine (2×20 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography (silica gel, Hexanes/EtOAc/9:1 MeOH/NH4OH, 1:1:0 to 9:9:2)

Sources & evidence

ORD record
ord-6dd5b0bc4f5b462380d073609b734362
Source dataset
uspto-grants-2012_09
Patent number
US08268868B2

Reaction notes

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