Sodium hydride → 3-Tert-butyl-1-[6-(2,6-dichlorophenyl)-2-{[3-(morpholin-4-yl)propyl]amino}pyrido[2,3-d]pyrimidin-7-yl]urea

HRID 3443

Reaction equation

HRID 3443 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][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:15]=[CH:16][C:11]=2[CH:10]=1.[H-].[Na+].[C:32]([N:36]=[C:37]=[O:38])([CH3:35])([CH3:34])[CH3:33]>CN(C=O)C>[C:32]([NH:36][C:37]([NH:29][C:28]1[C:9]([C:3]2[C:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])=[CH:10][C:11]2[CH:16]=[N:15][C:14]([NH:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[N:13][C:12]=2[N:27]=1)=[O:38])([CH3:35])([CH3:34])[CH3:33]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 62412tert-Butyl isocyanateHCID 53281446-Arylpyrido[2,3-d]pyrimidine deriv. 42

Product 1

HCID 53281453-Tert-butyl-1-[6-(2,6-dichlorophenyl)-2-{[3-(morpholin-4-yl)propyl]amino}pyrido[2,3-d]pyrimidin-7-yl]ureaYield 79.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(2,6-dichlorophenyl)-N2 -(3-morpholin-4-yl-propyl)-pyrido[2,3-d]pyrimidine-2,7-diamine (1.0 g) from Example 58 in DMF (15 mL) was added one equivalent of 60% sodium hydride suspension (0.92 g). After stirring for approximately 1 hour at room temperature, one equivalent of tert-butyl isocyanate (0.230 g) was added, and the reaction was monitored by thin layer chromatography. After approximately 4 hours, the solvent was removed in vacuo. The residue was partitioned between ethyl acetate and water. The aqueous layer was washed several times with ethyl acetate. The ethyl acetate layers were combined, dried with magnesium sulfate, and concentrated in vacuo. Chromatography of the residue on silica gel using ethyl acetate followed by ethyl acetate:ethanol:triethylamine (18:2:1) gave 0.98 g of the title compound 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-(3-morpholin-4-yl-propylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea, CIMS (1% NH3 in CH4): 532=M+ +H, 531=M+,433, 84 (Base); mp 236°-240° C.

Workup

  1. waitAfter approximately 4 hours
  2. customthe solvent was removed in vacuo
  3. customThe residue was partitioned between ethyl acetate and water
  4. washThe aqueous layer was washed several times with ethyl acetate
  5. dry with materialdried with magnesium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ede167eccc134bd3a388eacac4ece473
Source dataset
uspto-grants-1998_03
Patent number
US05733913

Linked notes

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