Nitrogen → Tert-butyl-3-chloro-14-cyclohexyl-6-[2-(dimethylamino)ethyl]-7-oxo-5,6,7,8-tetrahydroindolo[2,1-a][2,5]benzodiazocine-11-carboxylate

HRID 1714008Notes

Reaction equation

HRID 1714008 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:16]=[C:15]2[C:11]([C:12]([CH:36]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)=[C:13](Br)[N:14]2[CH2:17][C:18]([N:20]([CH2:26][C:27]2[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=2Br)[CH2:21][CH2:22][N:23]([CH3:25])[CH3:24])=[O:19])=[CH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+].N#N>CN(C=O)C.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6]([C:8]1[CH:9]=[CH:10][C:11]2[C:12]([CH:36]3[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]3)=[C:13]3[C:28]4[CH:29]=[CH:30][C:31]([Cl:33])=[CH:32][C:27]=4[CH2:26][N:20]([CH2:21][CH2:22][N:23]([CH3:25])[CH3:24])[C:18](=[O:19])[CH2:17][N:14]3[C:15]=2[CH:16]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 947NitrogenHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 68507168tert-butyl-2-bromo-1-(2-{(2-bromo-5-chlorobenzyl)[2-(dimethylamino)ethyl]amino}-2-oxoethyl)-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 68509559Tert-butyl-3-chloro-14-cyclohexyl-6-[2-(dimethylamino)ethyl]-7-oxo-5,6,7,8-tetrahydroindolo[2,1-a][2,5]benzodiazocine-11-carboxylate

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a Smith PROCESS VIAL™ (2-5 ml) charged with a magnetic stirring bar, tert-butyl-2-bromo-1-(2-{(2-bromo-5-chlorobenzyl)[2-(dimethylamino)ethyl]amino}-2-oxoethyl)-3-cyclohexyl-1H-indole-6-carboxylate (from Step 8, 1 eq) in DMF dry (0.02 M), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (1.1 eq), PdCl2(dppf) (0.03 eq) and potassium acetate (3 eq) were added. The vial was closed with its cap and filled with N2 and microwaved in a Smith PERSONAL SYNTHESIZER at 150° C. for 6 min. The solution was then diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, filtered and concentrated in vacuo to afford the crude that was filtered through a plug of silica (EtOAc:PE:Et3N) (5:5:0.1%) and used in the next step without further purification; MS (ES+) m/z 550 (M+H)+.

Workup

  1. additionTo a Smith PROCESS VIAL™ (2-5 ml) charged with a magnetic stirring bar
  2. additionwere added
  3. customThe vial was closed with its
  4. customcap
  5. custommicrowaved in a Smith PERSONAL SYNTHESIZER at 150° C. for 6 min
  6. washwashed with H2O and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto afford the crude that
  11. filtrationwas filtered through a plug of silica (EtOAc:PE:Et3N) (5:5:0.1%)
  12. customused in the next step without further purification

Sources & evidence

ORD record
ord-18a844b45a2145c7baf7dd4db18fa34e
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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