Acetic Anhydride → N-(6-(5-(3-(3,3-Dimethylbutyl)ureido)-4-fluoro-2-methylphenyl)-7-methylpyrido[2,3-d]pyrimidin-2-yl)acetamide

HRID 522743Notes

Reaction equation

HRID 522743 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH:11]=[C:10]([C:12]3[C:13]([CH3:29])=[CH:14][C:15]([F:28])=[C:16]([NH:18][C:19]([NH:21][CH2:22][CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:20])[CH:17]=3)[C:9]([CH3:30])=[N:8][C:6]=2[N:7]=1.CN(C1C=CC=CN=1)C.[C:40](OC(=O)C)(=[O:42])[CH3:41].C([O-])([O-])=O.[Na+].[Na+]>N1C=CC=CC=1.O.CO>[CH3:27][C:24]([CH3:25])([CH3:26])[CH2:23][CH2:22][NH:21][C:19](=[O:20])[NH:18][C:16]1[C:15]([F:28])=[CH:14][C:13]([CH3:29])=[C:12]([C:10]2[C:9]([CH3:30])=[N:8][C:6]3[N:7]=[C:2]([NH:1][C:40](=[O:42])[CH3:41])[N:3]=[CH:4][C:5]=3[CH:11]=2)[CH:17]=1

Participants

8

Reactant 4

HCID 7918Acetic AnhydrideHCID 10340Sodium CarbonateHCID 218852-DimethylaminopyridineHCID 71731206HCID 71731206, compound

Product 1

HCID 89814149N-(6-(5-(3-(3,3-Dimethylbutyl)ureido)-4-fluoro-2-methylphenyl)-7-methylpyrido[2,3-d]pyrimidin-2-yl)acetamideYield 30%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

Treat a cooled solution (0° C.) of 1-(5-(2-amino-7-methylpyrido[2,3-d]pyrimidin-6-yl)-2-fluoro-4-methylphenyl)-3-(3,3-dimethylbutyl)urea (0.167 g, 0.407 mmol) and catalytic dimethylaminopyridine (0.005 g, 0.041 mmol) in pyridine (4 mL) with acetic anhydride (0.269 ml, 2.85 mmol) and stir at RT overnight. Add saturated. Na2CO3 and MeOH and heat at 45° C. overnight. Treat the mixture with water, extract with 4:1 EtOAc/THF (3×), wash the combined organics with saturated. Na2CO3, then brine, dry over MgSO4, concentrate to dryness and purify via silica gel chromatography (15-100% EtOAc/Hexanes). Dissolve the resulting material in acetonitrile/H2O, freeze and lyophilize to afford the title compound as an off-white solid (55 mg, 30% yield). MS (m/z): 453.2 (M+1).

Workup

  1. extractionextract with 4:1 EtOAc/THF (3×)
  2. washwash the combined organics with saturated
  3. dry with materialNa2CO3, then brine, dry over MgSO4
  4. concentrationconcentrate to dryness
  5. custompurify via silica gel chromatography (15-100% EtOAc/Hexanes)
  6. dissolutionDissolve the resulting material in acetonitrile/H2O

Sources & evidence

ORD record
ord-99e317a8d5d64c09853e54123766e96a
Source dataset
uspto-grants-2016_05
Patent number
US09334267B2

Reaction notes

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