Cesium carbonate → 1-{6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-2-azetidinone

HRID 222719Notes

Reaction equation

HRID 222719 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[NH:7]1[CH2:10][CH2:9][C:8]1=[O:11].[CH:12]1([N:16]2[CH2:22][CH2:21][C:20]3[CH:23]=[CH:24][C:25]([O:27][C:28]4[CH:33]=[CH:32][C:31](I)=[CH:30][N:29]=4)=[CH:26][C:19]=3[CH2:18][CH2:17]2)[CH2:15][CH2:14][CH2:13]1.N[C@@H]1CCCC[C@H]1N>O1CCOCC1.[Cu]I>[CH:12]1([N:16]2[CH2:22][CH2:21][C:20]3[CH:23]=[CH:24][C:25]([O:27][C:28]4[N:29]=[CH:30][C:31]([N:7]5[CH2:10][CH2:9][C:8]5=[O:11])=[CH:32][CH:33]=4)=[CH:26][C:19]=3[CH2:18][CH2:17]2)[CH2:13][CH2:14][CH2:15]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 1367212-AzetidinoneHCID 574402941H-3-Benzazepine, 3-cyclobutyl-2,3,4,5-tetrahydro-7-[(5-iodo-2-pyridinyl)oxy]-

Product 1

HCID 103613561-{6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-2-azetidinone

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

Cesium carbonate (678 mg, 1.04 mmol) was added to a solution of 2-azetidinone (308 mg, 4.3 mmol) in dioxane (1 ml). The mixture was heated in a microwave reactor at 150° C. for 1 minute then a mixture of 3-cyclobutyl-7-[(5-iodo-2-pyridinyl)oxy]-2,3,4,5-tetrahydro-1H-3-benzazepine (E207) (294 mg, 0.7 mmol), trans-1,2-diaminocyclohexane (0.02 ml) and copper (I) iodide (126 mg, 1.2 mmol) were added and the resulting mixture was heated in microwave reactor at 180° C. for 1 hour. The reaction mixture was cooled and applied to a SCX cartridge (Varian bond-elute, 10 g) and washed with methanol and then a mixture of 0.880 ammonia:methanol (1:9). The combined basic fractions were concentrated in vacuo and the resulting residue purified by column chromatography (0.5:2.5:97.5) to afford the title compound (E219). MS (ES+) m/e 364 [M+H]+.

Workup

  1. additionwere added
  2. temperaturethe resulting mixture was heated in microwave reactor at 180° C. for 1 hour
  3. temperatureThe reaction mixture was cooled
  4. washwashed with methanol
  5. additiona mixture of 0.880 ammonia:methanol (1:9)
  6. concentrationThe combined basic fractions were concentrated in vacuo
  7. customthe resulting residue purified by column chromatography (0.5:2.5:97.5)

Sources & evidence

ORD record
ord-a6c2c6474cfa4806a471b9f3f1cf5538
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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