Potassium Carbonate → 2-methylpropan-2-yl 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzoate

HRID 1877510Notes

Reaction equation

HRID 1877510 reaction equation
C(=O)([O-])[O-].[K+].[K+].[NH2:7][CH:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[C:14]([C:16]1[N:21]=[CH:20][C:19]([C:22]2[C:34]3[C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[N:27]([C:35]4[CH:47]=[CH:46][C:38]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[C:37](F)[CH:36]=4)[C:26]=3[CH:25]=[CH:24][CH:23]=2)=[CH:18][CH:17]=1)#[N:15]>CS(C)=O.O>[C:14]([C:16]1[N:21]=[CH:20][C:19]([C:22]2[C:34]3[C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[N:27]([C:35]4[CH:36]=[CH:37][C:38]([C:39]([O:41][C:42]([CH3:43])([CH3:44])[CH3:45])=[O:40])=[C:46]([NH:7][CH:8]5[CH2:13][CH2:12][O:11][CH2:10][CH2:9]5)[CH:47]=4)[C:26]=3[CH:25]=[CH:24][CH:23]=2)=[CH:18][CH:17]=1)#[N:15]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 4192234-AminotetrahydropyranHCID 583382932-methylpropan-2-yl 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-fluorobenzoate

Product 1

HCID 673084902-methylpropan-2-yl 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzoateYield 40.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

0.95 g of potassium carbonate and 4.62 g of 4-aminotetrahydropyran are successively added to a solution of 1.06 g of 2-methylpropan-2-yl 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-fluorobenzoate, obtained in stage 1 of Example 49, in 8 ml of dimethyl sulphoxide. The reaction mixture is heated at 90° C. for 3 hours in a microwave, and then diluted with distilled water. The aqueous phase is washed twice with ethyl acetate and the combined organic phases are washed with water and a saturated solution of sodium chloride, dried over magnesium sulphate and filtered. The residue is purified by silica gel chromatography, elution being carried out with a mixture of cyclohexane and ethyl acetate (85/15 by volume), so as to give 0.5 g of 2-methylpropan-2-yl 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzoate in the form of a white foam, the characteristics of which are the following:

Workup

  1. washThe aqueous phase is washed twice with ethyl acetate
  2. washthe combined organic phases are washed with water
  3. dry with materiala saturated solution of sodium chloride, dried over magnesium sulphate
  4. filtrationfiltered
  5. customThe residue is purified by silica gel chromatography, elution
  6. additionbeing carried out with a mixture of cyclohexane and ethyl acetate (85/15 by volume)

Sources & evidence

ORD record
ord-d2de6989f2a64d80973ecdf25409f4bf
Source dataset
uspto-grants-2012_11
Patent number
US08309721B2

Reaction notes

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