4,4,5,5-Tetramethyl[1,3,2]dioxaborolane → tert-butyl 6-(8-(benzo[d]thiazol2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate

HRID 1778827Notes

Reaction equation

HRID 1778827 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[N:28]=[C:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:26](Br)=[CH:25][CH:24]=1)[CH2:19][CH2:18]2)=[O:12].[CH3:37][C:38]1([CH3:45])[C:42]([CH3:44])([CH3:43])[O:41][BH:40][O:39]1>O1CCCC1.C(N(CC)CC)C.CC#N.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].ClCCl>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[N:28]=[C:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:26]([B:40]3[O:41][C:42]([CH3:44])([CH3:43])[C:38]([CH3:45])([CH3:37])[O:39]3)=[CH:25][CH:24]=1)[CH2:19][CH2:18]2)=[O:12]

Participants

7

Reactant 2

HCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 594476151,1-Dimethylethyl 6-(8-((2-benzothiazolylamino)carbonyl)-3,4-dihydro-2(1H)-isoquinolinyl)-3-bromo-2-pyridinecarboxylate

Product 1

HCID 89498009tert-butyl 6-(8-(benzo[d]thiazol2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of EXAMPLE 1D (1.2 g), 1.0 M 4,4,5,5-tetramethyl-1,3,2-dioxaborolane in tetrahydrofuran (4.24 mL), triethylamine (0.92 mL), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane (0.087 g) in CH3CN (15 mL) was heated at 100° C. in a Biotage Initiator microwave reactor for 30 minutes. After cooling, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was extracted with additional ethyl acetate twice. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel to provide the title compound.

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between water and ethyl acetate
  3. extractionThe organic layer was extracted with additional ethyl acetate twice
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-2d93d92f92a3462bb4769ee861830935
Source dataset
uspto-grants-2016_02
Patent number
US09266877B2

Reaction notes

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