Tributylvinyltin → HCID 86668114, compound

HRID 474266Notes

Reaction equation

HRID 474266 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[CH2:19]([Sn](CCCC)(CCCC)C=C)[CH2:20]CC.[NH2:34][CH2:35][CH2:36][O:37][C:38]1[CH:45]=[C:44]([N+:46]([O-:48])=[O:47])[CH:43]=[CH:42][C:39]=1[C:40]#[N:41]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:3]=[C:4]([CH2:19][CH2:20][NH:34][CH2:35][CH2:36][O:37][C:38]2[CH:45]=[C:44]([N+:46]([O-:48])=[O:47])[CH:43]=[CH:42][C:39]=2[C:40]#[N:41])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1

Participants

6

Reactant 3

HCID 81998TributylvinyltinHCID 580754242,4-Dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidineHCID 66665326HCID 66665326, compound

Product 1

HCID 86668114HCID 86668114, compoundYield 20.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (0.1 g, 0.353 mmol), tributylethenylstannane (0.118 g, 0.371 mmol), tetrakis(triphenylphosphine)palladium (0.0081 g, 0.0070 mmol) in toluene (20 mL) was refluxed at 110° C. for 2 h under nitrogen. The solvent was removed under reduced pressure (high vacuum) and the residue was dissolved in 4 mL of THF/MeOH (3:1). 2-(2-Aminoethoxy)-4-nitrobenzonitrile (0.088 g, 0.424 mmol) was added and the mixture was refluxed at 75° C. for 18 h while monitoring by LC-MS. The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane (5 mL) and silica (1 g). The resultant slurry of the compound on silica was subjected to flash chromatography using a Teledyne Isco instrument (4 g RediSep silica column, 10% methanol in chloroform) to get 2-(2-((2-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)ethyl)amino)ethoxy)-4-nitrobenzonitrile (0.035 g, 20.56%) as a dark brown gummy liquid. LC-MS (M+H)+=482.0. 1H NMR: (400 MHz, CDCl3) δ ppm 7.93 (1H, d, J=8.4 Hz), 7.87 (1H, s), 7.74 (1H, d, J=8.4 Hz), 7.13-7.10 (2H, m), 7.02-6.98 (2H, m), 4.45-4.44 (2H, m), 4.36 (1H, t, J=8.4 Hz), 3.44-3.41 (4H, m), 3.11-3.09 (2H, m), 2.97-2.88 (2H, m), 2.74-2.66 (1H, m), 2.21-2.12 (1H, m).

Workup

  1. customThe solvent was removed under reduced pressure (high vacuum)
  2. dissolutionthe residue was dissolved in 4 mL of THF/MeOH (3:1)
  3. temperaturethe mixture was refluxed at 75° C. for 18 h while monitoring by LC-MS
  4. customThe solvent was removed under reduced pressure
  5. dissolutionthe residue was dissolved in dichloromethane (5 mL)

Sources & evidence

ORD record
ord-95a7715805824ad3827900596910581c
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Reaction notes

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