Methyl 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-iodopyrimidine-4-carboxylate → (E)-methyl 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-(2-(triethoxysilyl)vinyl)pyrimidine-4-carboxylate

HRID 244314Notes

Reaction equation

HRID 244314 reaction equation
[CH2:1]([O:3][Si:4]([O:23][CH2:24][CH3:25])([O:20][CH2:21][CH3:22])/[CH:5]=[CH:6]/[Sn](CCCC)(CCCC)CCCC)[CH3:2].[NH2:26][C:27]1[N:32]=[C:31]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([O:40][CH3:41])[C:34]=2[F:42])[N:30]=[C:29]([C:43]([O:45][CH3:46])=[O:44])[C:28]=1I>CN(C)C=O.O>[NH2:26][C:27]1[N:32]=[C:31]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([O:40][CH3:41])[C:34]=2[F:42])[N:30]=[C:29]([C:43]([O:45][CH3:46])=[O:44])[C:28]=1/[CH:6]=[CH:5]/[Si:4]([O:3][CH2:1][CH3:2])([O:20][CH2:21][CH3:22])[O:23][CH2:24][CH3:25]

Participants

5

Reactant 2

HCID 70497072Methyl 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-iodopyrimidine-4-carboxylateHCID 86668310(E)-triethoxy(2-(tributylstannyl)vinyl)silane

Product 1

HCID 70497970(E)-methyl 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-(2-(triethoxysilyl)vinyl)pyrimidine-4-carboxylateYield 6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Tetrakis triphenylphosphine palladium(0) (160 mg, 0.14 mmol, 0.10 equiv) and (E)-triethoxy(2-(tributylstannyl)vinyl)silane (990 mg, 2.1 mmol, 1.5 equiv) were sequentially added to a stirred solution of methyl 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-iodopyrimidine-4-carboxylate (600 mg, 1.4 mmol, 1.0 equiv) in N,N-dimethylformamide (5.5 mL) at room temperature. The heterogeneous yellow mixture was heated at 90° C. and stirred for 5 d. The cooled reaction mixture was diluted with water (300 mL) and extracted with diethyl ether (3×100 mL). The combined organic layers were dried (magnesium sulfate), gravity filtered, and concentrated under vacuum. The product was purified by acid free reverse phase column chromatography (5% acetonitrile to 100% acetonitrile gradient) to provide the title compound as a yellow glass (38 mg, 6% yield): IR (thin film) 3315 (w), 3069 (w), 2974 (w), 1657 (s) cm−1; 1H NMR (400 MHz, CDCl3) δ 7.66 (dd, J=9, 8 Hz, 1H), 7.29 (d, J=18.5 Hz, 1H), 7.21 (dd, J=9, 2 Hz, 1H), 6.06 (d, J=18.5 Hz, 1H), 5.39 (br s, 2H), 3.98 (d, J=1 Hz, 3H), 3.92 (s, 3H), 3.89 (q, J=7 Hz, 6H), 1.26 (t, J=7 Hz, 9H); ESIMS m/z 500 [(M+H)+].

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with diethyl ether (3×100 mL)
  3. dry with materialThe combined organic layers were dried (magnesium sulfate), gravity
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe product was purified by acid free reverse phase column chromatography (5% acetonitrile to 100% acetonitrile gradient)

Sources & evidence

ORD record
ord-49256f6a0ab34167b466b49230818a98
Source dataset
uspto-grants-2014_02
Patent number
US08658568B2

Reaction notes

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