Tributylvinyltin → HCID 59860362, compound

HRID 252122Notes

Reaction equation

HRID 252122 reaction equation
Cl.[Cl:2][C:3]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:4]=1[CH2:5][NH:6][C@H:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][C:15](I)=[CH:14][N:13]=2)[CH2:8]1.[CH2:24]([Sn](CCCC)(CCCC)C=C)[CH2:25]CC>CN(C=O)C.C(N(CC)CC)C.Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:2][C:3]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:4]=1[CH2:5][NH:6][C@H:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][C:15]([CH:24]=[CH2:25])=[CH:14][N:13]=2)[CH2:8]1

Participants

7

Reactant 2

HCID 81998TributylvinyltinHCID 66854640HCID 66854640, compound

Product 1

HCID 59860362HCID 59860362, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
65 °C

Procedure

Dissolve (S)-(2,4-dichlorobenzyl)-[1-(5-iodopyridin-2-yl)-pyrrolidin-3-yl]-amine hydrochloride (200 mg, 0.41 mmol) in DMF (7 mL) and triethylamine (60 μL). Add tetrakis(triphenylphosphine)palladium (0) (24 mg, 0.021 mmol) and tributyl(vinyl)tin (150 μL, 0.49 mmol). Heat the mixture at 65° C. overnight. Cool to room temperature, dilute with 1 N HCl (15 mL). Wash the mixture with dichloromethane (3×). Basify the aqueous solution to about pH=9 by adding solid potassium carbonate. Extract with dichloromethane (3×), dry (magnesium sulfate), concentrate and chromatograph on silica gel, eluting with 10:90 to 1:1 ethyl acetate:hexanes, to give the title compound as a residue. Dissolve the residue in methanol, add 1 N HCl in methanol (1 mL). Concentrate and dry in a vacuum oven at 60° C. to give the title compound as its hydrochloride salt (97 mg, 56%): 1H NMR (400 MHz, MeOH-d4) 8.30 (dd, 1H, J=8.8, 2.0 Hz), 7.97 (d, 1H, J=2.4 Hz), 7.71 (d, 1H, J=8.0 Hz), 7.68 (d, 1H, J=1.6 Hz), 7.50 (dd, 1H, J=8.0, 2.2 Hz), 7.16 (d, 1H, J=9.2 Hz), 6.70 (dd, 1H, J=17.6, 11.2 Hz), 5.87 (d, 1H, J=17.6 Hz), 5.40 (d, 1H, J=11.2 Hz), 4.55-4.47 (m, 2H), 4.34-4.28 (m, 1H), 4.18-4.13 (m, 1H), 3.97-3.91 (m, 2H), 3.80-3.74 (m, 1H), 2.77-2.68 (m, 1H), 2.55-2.46 (m, 1H), MS (ES): m/z 348 [M+H].

Workup

  1. temperatureCool to room temperature
  2. washWash the mixture with dichloromethane (3×)
  3. additionBasify the aqueous solution to about pH=9 by adding solid potassium carbonate
  4. extractionExtract with dichloromethane (3×)
  5. dry with materialdry (magnesium sulfate)
  6. concentrationconcentrate
  7. washchromatograph on silica gel, eluting with 10:90 to 1:1 ethyl acetate

Sources & evidence

ORD record
ord-9a92324989b742efbc9894d6f47b1ac7
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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