Cesium carbonate → HCID 86655136, compound

HRID 1045921Notes

Reaction equation

HRID 1045921 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([Cl:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[C:16]2[C:17](=[O:23])[N:18]([CH3:22])[CH2:19][CH2:20][O:21][C:15]=2[CH:14]=[CH:13][CH:12]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([NH:10][C:11]2[C:16]3[C:17](=[O:23])[N:18]([CH3:22])[CH2:19][CH2:20][O:21][C:15]=3[CH:14]=[CH:13][CH:12]=2)[C:5]([Cl:9])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 534009652,5-Dichloro-4-iodopyridineHCID 67075766HCID 67075766, compound

Product 1

HCID 86655136HCID 86655136, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2,5-Dichloro-4-iodopyridine (0.2 g, 0.73 mmol), 6-amino-4-methyl-2,3-dihydro-1,4-benzoxazepin-5-one (0.140 g, 0.73 mmol), palladium(II) acetate (6.56 mg, 0.03 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.025 g, 0.04 mmol) and cesium carbonate (0.476 g, 1.46 mmol) were suspended in dioxane (5 mL). The mixture was heated at 100° C. for 30 minutes in a microwave reactor and then allowed to cool to room temperature. The mixture was loaded onto an SCX column and the product eluted first with MeOH and then with a 7M solution of NH3 in MeOH. Fractions containing product were combined and evaporated. The residue was purified by chromatography on silica, eluting with a gradient of 0-5% MeOH in CH2Cl2. Fractions containing product were combined and evaporated to afford 6-[(2,5-dichloropyridin-4-yl)amino]-4-methyl-2,3-dihydro-1,4-benzoxazepin-5-one (0.118 g, 48% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 3.10 (3H, s), 3.55 (2H, t), 4.34 (2H, t), 6.88-6.91 (1H, m), 7.13 (1H, s), 7.36-7.39 (1H, m), 7.50 (1H, t), 8.26 (1H, s), 9.31 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+ =337.96 and 339.99 and 341.96.

Workup

  1. temperatureto cool to room temperature
  2. washthe product eluted first with MeOH
  3. additionFractions containing product
  4. customevaporated
  5. customThe residue was purified by chromatography on silica
  6. washeluting with a gradient of 0-5% MeOH in CH2Cl2
  7. additionFractions containing product
  8. customevaporated

Sources & evidence

ORD record
ord-f6bd6027626f4c44bbca6539bf01eaac
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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