Cesium carbonate → tert-butyl 2-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)acetate

HRID 1466606Notes

Reaction equation

HRID 1466606 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[C:24]4[N:23]=[CH:22]N=CC=4NN=3)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:7]=1.[C:27]([O:31][C:32](=[O:35])[CH2:33]Br)([CH3:30])([CH3:29])[CH3:28].C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])[O-]>CCOC(C)=O.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:11]=[N:10][N:9]4[CH:8]=[CH:6][CH:22]=[N:23][C:24]=34)=[O:15])=[CH:11][N:10]([CH2:33][C:32]([O:31][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:35])[N:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 19660Carbonate IonHCID 79177tert-Butyl bromoacetate2×HCID 178490636HCID 178490636, compound

Product 1

HCID 66900073tert-butyl 2-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)acetateYield 141.9%

Reagents, catalysts & solvents 1

HCID 22728543Water ethylacetateSolvent

Conditions

Temperature
30 °C

Procedure

N-(3-(5-chloro-2-methoxyphenyl)-1H-pyrazol-4-yl)pyrazolo pyrimidine-3-carboxamide (2.0 g, 5.4 mmol), t-butyl-bromoacetate (0.88 mL, 6.0 mmol), and cesium carbonate (2.1 g, 6.5 mmol) were combined and stirred at 30° C. overnight. The mixture was warmed to 65° C. at which time additional carbonate and t-butylbromoacetate was added and stirred 8 hrs. The mixture was cooled to ambient temperature and stirred overnight, then partitioned EtOAc/water. The organic phase was separated, washed with brine, dried (Na2SO4), filtered through silica gel, and concentrated to a solid. The solid was washed with 1:1 EtOAc/hexanes to yield 1.85 g (71%) of tert-butyl 2-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)acetate as yellow crystals. LCMS (ESI) m+H=483.0. 1H NMR (400 MHz, CDCl3) δ 9.74 (s, 1H), 8.77 (m, 1H), 8.73 (s, 1H), 8.51 (m, 1H0, 8.38 (s, 1H), 8.02 (s, 1H), 7.58 (s, 1H), 7.31 (m, 1H), 6.97 (m, 2H), 4.85 (s, 2H), 3.83 (s, 3H), 1.49 (s, 9H).

Workup

  1. additionwas added
  2. stirringstirred 8 hrs
  3. temperatureThe mixture was cooled to ambient temperature
  4. stirringstirred overnight
  5. customThe organic phase was separated
  6. washwashed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered through silica gel
  9. concentrationconcentrated to a solid
  10. washThe solid was washed with 1:1 EtOAc/hexanes

Sources & evidence

ORD record
ord-015c64253466459985697793754c418d
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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