Stannane, tributyl(1-ethoxyethenyl)- → HCID 71549177, compound

HRID 1848101Notes

Reaction equation

HRID 1848101 reaction equation
Br[C:2]1[CH:28]=[CH:27][C:5]2[N:6]([CH2:9][C:10]3[CH:26]=[CH:25][C:13]4[N:14]=[C:15]([NH:17][C@@H:18]5[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]5[OH:24])[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.C([Sn](CCCC)(CCCC)[C:34]([O:36]CC)=[CH2:35])CCC>CC(N(C)C)=O.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]>[OH:24][C@@H:19]1[CH2:20][CH2:21][CH2:22][CH2:23][C@H:18]1[NH:17][C:15]1[S:16][C:12]2[CH:11]=[C:10]([CH2:9][N:6]3[C:5]4[CH:27]=[CH:28][C:2]([C:34](=[O:36])[CH3:35])=[CH:3][C:4]=4[N:8]=[CH:7]3)[CH:26]=[CH:25][C:13]=2[N:14]=1

Participants

5

Reactant 2

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 71549044HCID 71549044, compound

Product 1

HCID 71549177HCID 71549177, compoundYield 8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

A stirred suspension of (1R,2R)-2-((6-((5-bromo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (150 mg, 0.33 mmol) from Step 5 of Example 108 and tributyl(1-ethoxyvinyl)tin (177 mg, 0.5 mmol) in DMA (1.5 mL) was purged with a stream of argon for 5 min. To the mixture was added tetrakis(triphenylphosphine)palladium (0) (57 mg, 0.05 mmol) and argon was bubbled into the mixture for an additional 5 min. The reaction vessel was sealed and the mixture was heated at 110° C. for 3 h. The mixture was cooled to rt. To the mixture was added 0.5 M aq HCl (500 μL) followed by stirring at rt for 12 h. The mixture was filtered, and the filtrate was purified directly by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and a Varian Pursuit XRs C18 column as the stationary phase. The product was further purified by silica gel flash chromatography eluting with 5% MeOH in CH2Cl2 to afford 1-(1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)ethanone (11 mg, 8%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ 8.57 (s, 1H), 8.32 (s, 1H), 7.97 (d, J=7.5 Hz, 1H), 7.85 (d, J=8.5 Hz, 1H), 7.64-7.72 (m, 2H), 7.30 (m, 1H), 7.20 (m, 1H), 5.52 (s, 2H), 4.73 (d, J=5.1 Hz, 1H), 3.52 (m, 1H), 3.34 (m, 1H), 2.62 (s, 3H), 2.02 (m, 1H), 1.90 (m, 1H), 1.55-1.69 (m, 2H), 1.10-1.35 (m, 4H); LCMS (ESI) m/z 421 (M+H)+.

Workup

  1. customwas purged with a stream of argon for 5 min
  2. customwas bubbled into the mixture for an additional 5 min
  3. customThe reaction vessel was sealed
  4. temperatureThe mixture was cooled to rt
  5. additionTo the mixture was added 0.5 M aq HCl (500 μL)
  6. filtrationThe mixture was filtered
  7. customthe filtrate was purified directly by reverse-phase preparative HPLC
  8. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase
  9. customThe product was further purified by silica gel flash chromatography
  10. washeluting with 5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-9b7ba14abbf540a0ae40419c597663b0
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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