Cesium carbonate → HCID 68660645, compound

HRID 576095Notes

Reaction equation

HRID 576095 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[C:12](=[CH:13][C:14](B4OC(C)(C)C(C)(C)O4)=[CH:15][CH:16]=3)[CH2:11][N:10]([CH3:27])[CH2:9]2)=[CH:4][CH:3]=1.Cl[C:29]1[N:34]=[N:33][C:32]([N:35]([CH3:43])[C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:31][CH:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)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]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[C:12](=[CH:13][C:14]([C:29]4[N:34]=[N:33][C:32]([N:35]([CH3:43])[C:36](=[O:42])[O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[CH:31][CH:30]=4)=[CH:15][CH:16]=3)[CH2:11][N:10]([CH3:27])[CH2:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 66788541HCID 66788541, compoundHCID 86647717HCID 86647717, compound

Product 1

HCID 68660645HCID 68660645, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of 4-(4-fluorophenyl)-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline (1.13 g, 3.08 mmol), and tert-butyl 6-chloropyridazin-3-yl(methyl)carbamate (751 mg, 3.08 mmol) in DMF (15 mL) and water (3 mL) was added cesium carbonate (4.01 g, 12.3 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (50 mg, 0.06 mmol). The reaction flask was evacuated and back filled with nitrogen. After heating the reaction mixture at 85° C. for 4 hours, it was cooled to ambient temperature then partitioned between ethyl acetate (300 mL) and water (150 mL). The organic layer was washed with water and brine then dried over sodium sulfate. Concentration in vacuo gave the crude material which was purified by flash column chromatography to give tert-butyl 6-(4-(4-fluorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyridazin-3-yl(methyl)carbamate (1.24 g, 90%) as an orange/brown foam: 1H NMR (CDCl3, 500 MHz) δ 8.12 (d, J=9.5 Hz, 1H), 7.88 (d, J=1.5 Hz, 1H), 7.75-7.70 (m, 2H), 7.19 (dd, J=8.8 Hz, 5.0 Hz, 2H), 7.01-6.97 (m, 3H), 4.30 ((brs, 1H), 3.82 (d, J=14.5 Hz, 1H), 3.71 (d, J=14.5 Hz, 1H), 3.61 (s, 3H), 3.08-3.05 (m, 1H), 2.59 (dd, J=11.5 Hz, 8.0 Hz, 1H), 2.46 (s, 3H), 1.56 (s, 9H); ESI MS m/z 449 [M+H]+.

Workup

  1. customThe reaction flask was evacuated
  2. additionback filled with nitrogen
  3. temperatureit was cooled to ambient temperature
  4. customthen partitioned between ethyl acetate (300 mL) and water (150 mL)
  5. washThe organic layer was washed with water and brine
  6. dry with materialthen dried over sodium sulfate
  7. concentrationConcentration in vacuo
  8. customgave the crude material which
  9. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-2ddd4f696e5d4b7d890b8643160ea26c
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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