Dimethylformamide → 1-Tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[4-(diethylamino)butylamino]pyrido[2,3-d]pyrimidin-7-yl]urea

HRID 617997Notes

Reaction equation

HRID 617997 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:28]([NH2:29])=[N:27][C:12]2[N:13]=[C:14]([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[N:15]=[CH:16][C:11]=2[CH:10]=1.[H-].[Na+].[C:32]1([N:38]=[C:39]=[O:40])[CH:37]=CC=C[CH:33]=1.[CH3:41]N(C=O)C>>[C:32]([NH:38][C:39]([NH:29][C:28]1[C:9]([C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=2[Cl:8])=[CH:10][C:11]2[CH:16]=[N:15][C:14]([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[N:13][C:12]=2[N:27]=1)=[O:40])([CH3:41])([CH3:37])[CH3:33]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 7672Phenyl isocyanateHCID 24758Sodium hydrideHCID 53281336-(2,6-dichlorophenyl)-2-N-[4-(diethylamino)butyl]pyrido[2,3-d]pyrimidine-2,7-diamine

Product 1

HCID 53281351-Tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[4-(diethylamino)butylamino]pyrido[2,3-d]pyrimidin-7-yl]urea

Procedure

To a solution of 6-(2,6-dichlorophenyl)-N2 -(4-diethylamino-butyl)-pyrido[2,3-d]pyrimidine-2,7-diamine (25.0 g) from Example 53 in DMF (300 mL) was added 1 equivalent of 60% sodium hydride suspension (2.31 g). After stirring for approximately 2 hours at room temperature, one equivalent of phenyl isocyanate (5.72 g) was added and the reaction monitored by thin layer chromatography After approximately 24 hours, the solvent was removed in vacuo. The residue was dissolved in dichloromethane and this solution was washed several times, first with water and then a saturated solution of sodium chloride. The dichloromethane layer was dried with magnesium sulfate and concentrated in vacuo. Chromatography of the residue on silica gel eluting with ethyl acetate:ethanol:triethylamine (9:2:1), followed by crystallization from tert-butyl methyl ester gave 21.58 g of the title compound 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-(4-diethylamino-butylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea, ESMS (20/80 MeOH/CH3CN+0.1% AcOH): M+ +H=532; mp dec 157° C.

Workup

  1. waitthe reaction monitored by thin layer chromatography After approximately 24 hours
  2. customthe solvent was removed in vacuo
  3. dissolutionThe residue was dissolved in dichloromethane
  4. washthis solution was washed several times
  5. dry with materialThe dichloromethane layer was dried with magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customChromatography of the residue on silica gel eluting with ethyl acetate:ethanol:triethylamine (9:2:1), followed by crystallization from tert-butyl methyl ester

Sources & evidence

ORD record
ord-6fb287bcd3e849c8a039fdac389795d2
Source dataset
uspto-grants-1999_09
Patent number
US05952342

Reaction notes

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