Potassium Carbonate → HCID 46926846, compound

HRID 1184493Notes

Reaction equation

HRID 1184493 reaction equation
[CH3:1][CH:2]1[O:7][C:6]2[C:8]([CH2:19][CH2:20][CH3:21])=[CH:9][C:10]([CH2:12][N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[CH:11][C:5]=2[NH:4][C:3]1=[O:22].F[C:24]1[CH:33]=[CH:32][C:27]([C:28]([NH:30][CH3:31])=[O:29])=[CH:26][CH:25]=1.C1CCN2C(=NCCC2)CC1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[CH3:31][NH:30][C:28](=[O:29])[C:27]1[CH:32]=[CH:33][C:24]([N:16]2[CH2:15][CH2:14][N:13]([CH2:12][C:10]3[CH:9]=[C:8]([CH2:19][CH2:20][CH3:21])[C:6]4[O:7][CH:2]([CH3:1])[C:3](=[O:22])[NH:4][C:5]=4[CH:11]=3)[CH2:18][CH2:17]2)=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 40742474-fluoro-N-methylbenzamideHCID 66716780HCID 66716780, compound

Product 1

HCID 46926846HCID 46926846, compoundYield 18.67%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

In a 20 mL scintillation vial was added 2-methyl-6-(piperazin-1-ylmethyl)-8-propyl-2H-benzo[b][1,4]oxazin-3(4H)-one 358E (67 mg, 0.221 mmol) and 4-fluoro-N-methylbenzamide (50.7 mg, 0.331 mmol) in DMSO (1.104 mL) and stirred at 120° C. for 4 h. DBU (0.133 mL, 0.883 mmol) was added and the reaction mixture was stirred at 120° C. for 18 h. The reaction was concentrated in vacuo to remove DBU, and then K2CO3 (61.0 mg, 0.442 mmol) was added. The mixture was heated overnight at 120° C. The reaction was subsequently filtered and the crude material was purified by prep HPLC 20-45% acetonitrile in water. The appropriate fractions were collected and concentrated in vacuo to give the title compound as a yellow solid (18 mg, 0.041 mmol, 18.67% yield). 1H NMR (DMSO-d6, 400 MHz): δ=10.89 (s, 1H), 10.73 (br. s., 1H), 8.04 (br. s., 1H), 7.75 (d, J=8.8 Hz, 1H), 7.24 (s, 1H), 7.11 (s, 1H), 6.95-7.04 (m, 2H), 6.87 (d, J=2.0 Hz, 1H), 4.66-4.72 (m, 1H), 4.64 (d, J=6.6 Hz, 2H), 3.26 (t, J=7.1 Hz, 2H), 3.03 (q, J=6.7 Hz, 2H), 2.30-2.45 (m, 3H), 1.61-1.67 (m, 2H), 1.55 (d, J=6.8 Hz, 5H), 1.40 (d, J=6.8 Hz, 3H), 0.86-0.93 ppm (m, 3H). ESI-MS: m/z 437.4 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at 120° C. for 18 h
  2. concentrationThe reaction was concentrated in vacuo
  3. customto remove DBU
  4. temperatureThe mixture was heated overnight at 120° C
  5. filtrationThe reaction was subsequently filtered
  6. customthe crude material was purified by prep HPLC 20-45% acetonitrile in water
  7. customThe appropriate fractions were collected
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bfc228474cb546399f6b05d4ea2c8964
Source dataset
uspto-grants-2014_03
Patent number
US08669249B2

Reaction notes

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