Potassium Carbonate → 6-(4-{5-[(4-Fluorophenyl)methyl]pyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-3-nitropyridin-2-amine

HRID 241200Notes

Reaction equation

HRID 241200 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2C)=[CH:4][CH:3]=1.[NH2:30][C:31]1[C:36]([N+:37]([O-:39])=[O:38])=[CH:35][CH:34]=[C:33](Cl)[N:32]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:33]5[N:32]=[C:31]([NH2:30])[C:36]([N+:37]([O-:39])=[O:38])=[CH:35][CH:34]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][CH:14]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27240356-Chloro-3-nitropyridin-2-ylamineHCID 66820119(4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid

Product 1

HCID 668216706-(4-{5-[(4-Fluorophenyl)methyl]pyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-3-nitropyridin-2-amineYield 102.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (4-{5-[(4-fluorophenyl)methyl]pyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (example 8, step 2) (0.200 g, 0.509 mmol) and 2-amino-6-chloro-3-nitropyridine (0.106 g, 0.610 mmol) in dioxane (3 mL) and water (0.4 ml) was added potassium carbonate (0.211 g, 1.53 mmol). The solution was sparged with N2 (g) for five minutes before the addition of dichloro[1,1-bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (0.042 g, 10 mol %). The resulting suspension was heated at 90° C. for 20 h in a sealed tube vessel. On cooling to room temperature the mixture was diluted with acetonitrile (25 mL) then filtered and concentrated to afford 6-(4-{5-[(4-fluorophenyl)methyl]pyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-3-nitropyridin-2-amine (0.247 g, 100% yield) as an oil that was used without further purification. MS (EI) for C26H23FN6O3: 487 (MH+).

Workup

  1. customThe solution was sparged with N2 (g) for five minutes before the addition of dichloro[1,1-bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (0.042 g, 10 mol %)
  2. temperatureOn cooling to room temperature the mixture
  3. additionwas diluted with acetonitrile (25 mL)
  4. filtrationthen filtered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-b69280552e704a6281b6d7c3c398d03c
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

Loading…