6-bromo-8-cyclopentyl-5-methyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one → tert-Butyl 4-(6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido(2,3-d)pyrimidin-2-ylamino)-pyridin-3-yl)-piperazine-1-carboxylate

HRID 272425Notes

Reaction equation

HRID 272425 reaction equation
[Br:1][C:2]1[C:14](=[O:15])[N:13]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:5]2[N:6]=[C:7](S(C)=O)[N:8]=[CH:9][C:4]=2[C:3]=1[CH3:21].[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:36]=[N:37][C:38]([NH2:41])=[CH:39][CH:40]=2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]>C1(C)C=CC=CC=1.C(Cl)Cl>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:36]=[N:37][C:38]([NH:41][C:7]3[N:8]=[CH:9][C:4]4[C:3]([CH3:21])=[C:2]([Br:1])[C:14](=[O:15])[N:13]([CH:16]5[CH2:20][CH2:19][CH2:18][CH2:17]5)[C:5]=4[N:6]=3)=[CH:39][CH:40]=2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 2

HCID 113721276-bromo-8-cyclopentyl-5-methyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-oneHCID 11737525tert-Butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate

Product 1

HCID 11157536tert-Butyl 4-(6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido(2,3-d)pyrimidin-2-ylamino)-pyridin-3-yl)-piperazine-1-carboxylateYield 13%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

6-Bromo-8-cyclopentyl-2-methanesulfinyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (0.2 g, 0.54 mmol, prepared according to Example 5 in WO 01/70741) and 4-(6-Amino-pyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (0.6 g, 2.16 mmol) were combined in toluene (3 mL) and heated to 110° C. overnight. The reaction was quenched by the addition of succinic anhydride (0.2 g) and allowed to cool giving a solid. This solid was suspended in CH2Cl2 and filtered to give a white solid. The filtrate was washed with saturated aqueous sodium bicarbonate then saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The crude product was purified by silica gel chromatography eluting with 75% ethyl acetate:25% hexanes to provide 4-[6-(6-Bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.04 g, 13%). MS (APCI) M++1: Calc'd, 584.19. Found, 584.1.

Workup

  1. customThe reaction was quenched by the addition of succinic anhydride (0.2 g)
  2. temperatureto cool
  3. customgiving a solid
  4. filtrationfiltered
  5. customto give a white solid
  6. washThe filtrate was washed with saturated aqueous sodium bicarbonate
  7. dry with materialsaturated aqueous sodium chloride and dried over anhydrous magnesium sulfate
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with 75% ethyl acetate

Sources & evidence

ORD record
ord-706404dc5e034769a171df3d028583d5
Source dataset
uspto-grants-2008_11
Patent number
US07456168B2

Reaction notes

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