Tributylstannane → 3-[4-(8-Aza-bicyclo[3.2.1]oct-8-ylmethyl)-phenyl]-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1888484Notes

Reaction equation

HRID 1888484 reaction equation
[C:1]([C:3]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:7]3[N:20]=[CH:21][C:22]([C:24]4[CH:46]=[CH:45][C:27]([CH2:28][N:29]5[CH:34]6[CH2:35][CH2:36][CH:30]5[CH2:31][CH:32](OC(N5C=CN=C5)=S)[CH2:33]6)=[CH:26][CH:25]=4)=[CH:23][C:6]=3[C:5]=2[CH:4]=1)#[N:2].CC(N=NC(C#N)(C)C)(C#N)C.C([SnH](CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[CH:34]12[N:29]([CH2:28][C:27]3[CH:45]=[CH:46][C:24]([C:22]4[CH:21]=[N:20][C:7]5[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:17])([CH3:18])[CH3:19])[C:9]6[CH:10]=[N:11][C:3]([C:1]#[N:2])=[CH:4][C:5]=6[C:6]=5[CH:23]=4)=[CH:25][CH:26]=3)[CH:30]([CH2:36][CH2:35]1)[CH2:31][CH2:32][CH2:33]2

Participants

5

Reactant 3

HCID 5948TributylstannaneHCID 6547AzobisisobutyronitrileHCID 58266558Imidazole-1-carbothioic acid O-(8-{4-[6-cyano-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-3-yl]-benzyl}-8-aza-bicyclo[3.2.1]oct-3-yl)ester

Product 1

HCID 582665503-[4-(8-Aza-bicyclo[3.2.1]oct-8-ylmethyl)-phenyl]-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 84%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of imidazole-1-carbothioic acid O-(8-{4-[6-cyano-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-3-yl]-benzyl}-8-aza-bicyclo[3.2.1]oct-3-yl) ester (182 mg, 0.28 mmol) and AIBN (60 mg, 0.36 mmol) in toluene (10 mL) under an argon atmosphere was added tributyltin hydride (0.58 mL, 1.85 mmol). On complete addition, the reaction was heated at 110° C. for 15 minutes then allowed to cool to ambient temperature. The mixture was concentrated in vacuo and the resultant residue was purified by flash chromatography (silica, 50 g column, Biotage, 0-5% MeOH in DCM) to afford the title compound as a white solid (123 mg, 84%). 1H NMR (CDCl3, 300 MHz): 9.26 (d, J=1.0 Hz, 1H), 9.03 (d, J=2.2 Hz, 1H), 8.69 (d, J=2.2 Hz, 1H), 8.51 (d, J=1.0 Hz, 1H), 7.72-7.60 (m, 4H), 6.12 (s, 2H), 3.74-3.65 (m, 4H), 3.37-3.22 (m, 2H), 2.16-1.40 (m, 10H), 1.06-0.97 (m, 2H), 0.00 (s, 9H). LCMS (Method B): RT=2.96 min, M+H+=524.

Workup

  1. additionOn complete addition
  2. temperatureto cool to ambient temperature
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe resultant residue was purified by flash chromatography (silica, 50 g column, Biotage, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-52ad5fd180cf4c34be577acef13a5fa3
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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