Cesium carbonate → HCID 72706525, compound

HRID 929910Notes

Reaction equation

HRID 929910 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:20]=[N:21][N:22]([CH2:24][C:25]([NH:27][C@@H:28]([CH3:31])[CH2:29][OH:30])=[O:26])[CH:23]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=1[CH2:9][NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:18][C:19]2[CH:20]=[N:21][N:22]([CH2:24][C:25]([NH:27][C@@H:28]([CH3:31])[CH2:29][OH:30])=[O:26])[CH:23]=2)[N:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 90015329HCID 90015329, compoundHCID 90023132HCID 90023132, compound

Product 1

HCID 72706525HCID 72706525, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-chloro-N-(2,6-dichlorobenzyl)pyrimidin-4-amine (120 mg, 0.41 mmol), (S)-2-(4-amino-1H-pyrazol-1-yl)-N-(1-hydroxypropan-2-yl)acetamide V-1 (110 mg, 0.54 mmol, prepared by Procedure G1), Xantphos (47 mg, 0.08 mmol), Pd2dba3 (37 mg, 0.04 mmol) and cesium carbonate (333 mg, 1.02 mmol) in dioxane (40 mL) was heated to reflux under nitrogen. Upon completion, the reaction was concentrated in vacuo, diluted with aqueous sodium carbonate solution then extracted with ethyl acetate. The organic layer was dried (Na2SO4), concentrated in vacuo and purified by column chromatography (0-10% v/v [10% NH3 in MeOH]/DCM) to afford (S)-2-(4-((4-((2,6-dichlorobenzyl)amino)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-(1-hydroxypropan-2-yl)acetamide I-3 (60 mg, 25%). LC-MS (Method A), RT=8.32 min. (ES+) 450.

Workup

  1. temperaturewas heated
  2. temperatureto reflux under nitrogen
  3. concentrationUpon completion, the reaction was concentrated in vacuo
  4. additiondiluted with aqueous sodium carbonate solution
  5. extractionthen extracted with ethyl acetate
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography (0-10% v/v [10% NH3 in MeOH]/DCM)

Sources & evidence

ORD record
ord-29e7777c9a7b49be9d4e843cc368f6fd
Source dataset
uspto-grants-2016_03
Patent number
US09296725B2

Reaction notes

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