Toluene → (1-{6-[8-Cyclopentyl-6-(1-ethoxy-vinyl)-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]-pyridin-3-yl}-pyrrolidin-3-yl)-carbamic acid tert-butyl ester

HRID 586502Notes

Reaction equation

HRID 586502 reaction equation
[C:1]([O:5][C:6](=[O:38])[NH:7][CH:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:14]=[N:15][C:16]([NH:19][C:20]3[N:21]=[CH:22][C:23]4[C:29]([CH3:30])=[C:28](Br)[C:27](=[O:32])[N:26]([CH:33]5[CH2:37][CH2:36][CH2:35][CH2:34]5)[C:24]=4[N:25]=3)=[CH:17][CH:18]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC=CC=1.C([Sn](CCCC)(CCCC)[C:51]([O:53][CH2:54][CH3:55])=[CH2:52])CCC>C(Cl)(Cl)Cl.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6](=[O:38])[NH:7][CH:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:14]=[N:15][C:16]([NH:19][C:20]3[N:21]=[CH:22][C:23]4[C:29]([CH3:30])=[C:28]([C:51]([O:53][CH2:54][CH3:55])=[CH2:52])[C:27](=[O:32])[N:26]([CH:33]5[CH2:37][CH2:36][CH2:35][CH2:34]5)[C:24]=4[N:25]=3)=[CH:17][CH:18]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 1140TolueneHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 69210058{1-[6-(6-Bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-pyrrolidin-3-yl}-carbamic acid tert-butyl ester

Product 1

HCID 10196694(1-{6-[8-Cyclopentyl-6-(1-ethoxy-vinyl)-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]-pyridin-3-yl}-pyrrolidin-3-yl)-carbamic acid tert-butyl esterYield 104.6%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
110 °C

Procedure

A 6-dram vial was charged with {1-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-pyrrolidin-3-yl}-carbamic acid tert-butyl ester (379 mg, 0.65 mmol) and tetrakis(triphenylphosphine) palladium(0) (75 mg, 0.065 mmol) and the atmosphere replaced with argon. Toluene (5 ml) was added followed by tributyl-(1-ethoxy-vinyl)-stannane (352 mg, 0.97 mmol). The vial was heated to 110° C. and stirred for 12 h. The reaction mixture was diluted with chloroform (25 ml) and adsorbed onto silica gel. Chromatographic purification on silica gel (chloroform/2-propanol+1% TEA gradient) gave (1-{6-[8-cyclopentyl-6-(1-ethoxy-vinyl)-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]-pyridin-3-yl}-pyrrolidin-3-yl)-carbamic acid tert-butyl ester as a yellow solid (394 mg, 0.68 mmol). MS: (APCI+) 576 (M+1, 100), 548.

Workup

  1. customChromatographic purification on silica gel (chloroform/2-propanol+1% TEA gradient)

Sources & evidence

ORD record
ord-1b8070278faa4b08a3b6c9999b9588a6
Source dataset
uspto-grants-2005_08
Patent number
US06936612B2

Reaction notes

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