Cesium carbonate → HCID 86732446, compound

HRID 1776417Notes

Reaction equation

HRID 1776417 reaction equation
[CH3:1][O:2][C:3]1[CH:32]=[CH:31][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:17]3[N:22]=[C:21]([NH:23][C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)[C:20]([OH:30])=[CH:19][N:18]=3)=[N:9]2)=[CH:5][CH:4]=1.Br[CH:34]1[CH2:36][CH2:35]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.[Cu]Cl>[CH:34]1([O:30][C:20]2[C:21]([NH:23][C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)=[N:22][C:17]([C:10]3[C:11]4[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=4)[N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:32][CH:31]=4)[N:9]=3)=[N:18][CH:19]=2)[CH2:36][CH2:35]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 78037BromocyclopropaneHCID 136271303HCID 136271303, compound

Product 1

HCID 86732446HCID 86732446, compound

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

100 mg of 2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol (3-2, 0.236 mmol, 1. eq.), 34.2 mg of bromocyclopropane (0.283 mmol, 1.2 eq.), 44.9 mg of copper (I) chloride (0.236 mmol, 1 eq.) and 154 mg of cesium carbonate (0.471 mmol, 2 eq.) were suspended in 3 ml of dry DMF. The reaction mixture was stirred at 60° C. bath temperature for 18 hours. Then the mixture was partitioned between half saturated aq. ammonium chloride solution and dichloromethane/isopropanol 4:1. The phases were separated and the aqueous layer was extracted twice with dichloromethane/isopropanol 4:1. The combined organic layers were washed with brine including a precipitate which was separated with filtering it off. The precipitate was purified by preparative HPLC to yield 2.58 mg (0.047 mmol, 2%) of the analytically pure target compound.

Workup

  1. customThen the mixture was partitioned between half saturated aq. ammonium chloride solution and dichloromethane/isopropanol 4:1
  2. customThe phases were separated
  3. extractionthe aqueous layer was extracted twice with dichloromethane/isopropanol 4:1
  4. washThe combined organic layers were washed with brine including a precipitate which
  5. customwas separated
  6. filtrationwith filtering it off
  7. customThe precipitate was purified by preparative HPLC
  8. customto yield 2.58 mg (0.047 mmol, 2%) of the analytically pure target compound

Sources & evidence

ORD record
ord-39a29aee2d7d4d1483cfab1e4ecec28d
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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