Nitrogen → HCID 67814872, compound

HRID 2401395Notes

Reaction equation

HRID 2401395 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.N#N.Cl[C:14]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[C:18]2[C:25]([CH3:28])=[N:26][O:27][C:17]=2[CH:16]([C:29]([F:32])([F:31])[F:30])[N:15]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:14]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[C:18]3[C:25]([CH3:28])=[N:26][O:27][C:17]=3[CH:16]([C:29]([F:30])([F:32])[F:31])[N:15]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 67812971HCID 67812971, compound

Product 1

HCID 67814872HCID 67814872, compoundYield 49.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a resealable vial was added Pd(Ph3P)4 (20.33 mg, 0.018 mmol) and 4-fluorophenylboronic acid (49.2 mg, 0.352 mmol) before the vial was sealed and evacuated/backfilled with N2 (3×). To the vial was added 6-chloro-1-methyl-4-(trifluoromethyl)-4H-benzo[c]isoxazolo[4,5-e]azepine (52.9 mg, 0.176 mmol) dissolved in toluene (500 μL) and Na2CO3 (2M, 176 μl, 0.352 mmol). The solution was heated to 100° C. for 2 h before cooling to room temperature and diluting with water and EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude residue was purified via Biotage (EtOAc/hex) to afford the titled compound (31.2 mg, 0.087 mmol). LC/MS m/z 361 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 7.88 (d, J=7.1 Hz, 1H), 7.77 (dt, J=1.7, 7.5 Hz, 1H), 7.52-7.41 (m, 4H), 7.29-7.21 (m, 2H), 5.38 (q, J=7.6 Hz, 1H), 2.56 (s, 3H).

Workup

  1. temperaturebefore cooling to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified via Biotage (EtOAc/hex)

Sources & evidence

ORD record
ord-cc76ffd7ade84344ab28bf6db147555b
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

Loading…