Potassium Carbonate → 4-(3-{4-[(2E)-3-(2,5-Difluorophenyl)prop-2-en-1-yl]piperazin-1-yl}propyl)-6-methoxy-2H-1,4-benzoxazin-3(4H)-one

HRID 1644412Notes

Reaction equation

HRID 1644412 reaction equation
FC(F)(F)[C:3](O)=[O:4].[CH3:8][O:9][C:10]1[CH:29]=[CH:28][C:13]2CO[C:16](=[O:27])[N:17]([CH2:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:12]=2[CH:11]=1.C(N(CC)C(C)C)(C)C.Cl[CH2:40]/[CH:41]=[CH:42]/[C:43]1[CH:48]=[C:47]([F:49])[CH:46]=[CH:45][C:44]=1[F:50].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[F:50][C:44]1[CH:45]=[CH:46][C:47]([F:49])=[CH:48][C:43]=1/[CH:42]=[CH:41]/[CH2:40][N:24]1[CH2:23][CH2:22][N:21]([CH2:20][CH2:19][CH2:18][N:17]2[C:12]3[CH:11]=[C:10]([O:9][CH3:8])[CH:29]=[CH:28][C:13]=3[O:4][CH2:3][C:16]2=[O:27])[CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 11608064(E)-2-(3-Chloroprop-1-en-1-yl)-1,4-difluorobenzene2×HCID 667736227-Methoxy-1-(3-piperazin-1-ylpropyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one trifluoroacetate2×

Product 1

HCID 159822804-(3-{4-[(2E)-3-(2,5-Difluorophenyl)prop-2-en-1-yl]piperazin-1-yl}propyl)-6-methoxy-2H-1,4-benzoxazin-3(4H)-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 6-methoxy-4-(3-piperazin-1-ylpropyl)-2H-1,4-benzoxazin-3(4H)-one trifluoroacetate (Intermediate 118, 985 mg, 1.52 mmol) in dry ethanol (10 mL) was converted to the free base with N,N-diisopropylethylamine for 30 min and then was added 2-[(1E)-4-chloroprop-1-en-1-yl]-1,4-difluorobenzene (Intermediate 124, 315 mg, 1.67 mmol), and potassium carbonate (230 mg, 1.67 mmol). The mixture was heated at 80° C. for 18 hours, cooled to room temperature and then concentrated to dryness under reduced pressure. The residue was partitioned between water (50 mL) and dichloromethane (100 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure. Chromatography on silica gel with dichloromethane/methanol (95:5) gave the free base of the title compound as a yellow foam. The free base was taken up in dichloromethane (14 mL), followed by the addition of 2M HCl in ether (0.41 mL). The precipitate was collected by filtration and to give the bis hydrochloride salt of the product as a colorless solid, 171 mg (79%).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated to dryness under reduced pressure
  3. customThe residue was partitioned between water (50 mL) and dichloromethane (100 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b7357901cd694a74b98e2db1ffbe98ff
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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