2-(Methylthio)-4-(tributylstannyl)pyrimidine → 2-(S)-{[4-(4-Methoxy-phenoxy)-2'-methylsulfanyl-[2,4]bipyrimidin-yl-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1894151Notes

Reaction equation

HRID 1894151 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][NH:14][C:15]1[C:16]([O:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[N:17][C:18](Cl)=[N:19][CH:20]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:31][S:32][C:33]1[N:38]=[C:37]([Sn](CCCC)(CCCC)CCCC)[CH:36]=[CH:35][N:34]=1>O1CCOCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][NH:14][C:15]1[C:16]([O:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[N:17][C:18]([C:35]2[CH:36]=[CH:37][N:38]=[C:33]([S:32][CH3:31])[N:34]=2)=[N:19][CH:20]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 27632612-(Methylthio)-4-(tributylstannyl)pyrimidine2×HCID 582430462-(S)-{[2-Chloro-4-(4-methoxy-phenoxy)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 582474432-(S)-{[4-(4-Methoxy-phenoxy)-2'-methylsulfanyl-[2,4]bipyrimidin-yl-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl esterYield 50.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a teflon-lined septum-sealed Schlenk tube, a mixture of Compound 1e (213 mg; 0.49 mmol), 2-methylsulfanyl-4-tributylstannanyl-pyrimidine (Compound 7a) (305 mg; 0.735 mmol) and tetrakis-(triphenylphosphine)palladium(0) (57 mg; 0.049 mmol) in dioxane (1.0 mL) was irradiated in a Microwave reactor at 150° C. for 30 min. The resultant mixture was diluted with EtOAc, and washed with saturated NH4Cl(aq) and H2O. The organic phase was washed with H2O, and then dried over Na2SO4. The mixture was filtered and the filtrate was evaporated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a heptane-EtOAc gradient to afford Compound 7b (129 mg; 50% yield). 1H-NMR (400 MHz, CDCl3): δ 8.48-8.50 (m, 1H), 8.08-8.12 (m, 1H), 7.54-7.57 (m, 1H), 7.16-7.23 (m, 2H), 6.96-7.01 (m, 2H), 6.27 (br. s, 0.7H), 5.18 (br, 0.3H), 4.25-4.36 (m, 1H), 3.88 (s, 3H), 3.24-3.59 (m, 4H), 2.68 (s, 3H), 1.79-2.16 (m, 4H), 1.44-1.54 (m, 9H); MS: m/z 525.2 (M+H)+.

Workup

  1. customwas irradiated in a Microwave reactor at 150° C. for 30 min
  2. washwashed with saturated NH4Cl(aq) and H2O
  3. washThe organic phase was washed with H2O
  4. dry with materialdried over Na2SO4
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated under reduced pressure
  7. customto give the crude material
  8. customThe crude material was purified by flash column chromatography (SiO2)
  9. washeluting with a heptane-EtOAc gradient

Sources & evidence

ORD record
ord-5d1ed0c77e0e4434aa6e2fd74fddcc9a
Source dataset
uspto-grants-2013_08
Patent number
US08513271B2

Reaction notes

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