Methanol → Tasipimidine

HRID 1771417Notes

Reaction equation

HRID 1771417 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][O:6][CH:7]2[C:12]1[NH:13][CH2:14][CH2:15][N:16]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[C:38]([O-])([O-])=[O:39].[Cs+].[Cs+].CO>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:38][O:39][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][O:6][CH:7]2[C:12]1[NH:13][CH2:14][CH2:15][N:16]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 10796Cesium carbonateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 717669082-(5-bromoisochroman-1-yl)-4,5-dihydro-1H-imidazole

Product 1

HCID 71767208Tasipimidine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of 2-(5-bromoisochroman-1-yl)-4,5-dihydro-1H-imidazole (200 mg), 2-(di-t-butylphosphino)biphenyl (5.31 mg), palladium(II)acetate (3.19 mg) and Cs2CO3 (348 mg) was added methanol (1 ml) and toluene (2 ml). The mixture was degassed with N2 and then heated for 40 min at 120° C. and 30 min at 130° C. Alternatively, other Pd-ligand complexes and reaction conditions can be applied in the C—O formation. The title compound was purified by using separation methods E and G. (Yield 5 mg).

Workup

  1. customThe mixture was degassed with N2
  2. customAlternatively, other Pd-ligand complexes and reaction conditions
  3. customThe title compound was purified
  4. customseparation methods E and G

Sources & evidence

ORD record
ord-e5270498fdaa4c2cbcbcef4f0caff6a7
Source dataset
uspto-grants-2016_02
Patent number
US09249127B2

Reaction notes

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