Ethanol → HCID 89813524, compound

HRID 1051892Notes

Reaction equation

HRID 1051892 reaction equation
[CH:1]12[CH2:6][CH:5]1[CH2:4][N:3]([C:7]1[S:8][CH:9]=[C:10](Br)[N:11]=1)[CH2:2]2.C(O)C.[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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>[CH:1]12[CH2:6][CH:5]1[CH2:4][N:3]([C:7]1[S:8][CH:9]=[C:10]([C:20]3[CH:19]=[CH:18][C:17]([F:16])=[CH:22][C:21]=3[F:23])[N:11]=1)[CH2:2]2

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 898133372-(3-Azabicyclo[3.1.0]hexan-3-yl)-4-bromothiazole2×

Product 1

HCID 89813524HCID 89813524, compoundYield 77.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
92.5 °C

Procedure

To a solution of 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-bromothiazole (Step-1 of compound 66, 0.29 g, 1.16 mmol) in a mixture of toluene: ethanol (4 ml:16 ml) were added (2,4-difluorophenyl) boronic acid (0.20 g, 1.28 mmol) and potassium carbonate (0.32 g, 2.32 mmol) at 25° C. in a tube, the nitrogen gas was bubbled through reaction mixture for 15 minutes. To the reaction mixture was added tetrakis(triphenylphosphine)palladium(0) (0.067 g, 0.058 mmol) under nitrogen and the tube was sealed. The reaction mixture was heated at 90-95° C. for 18 hr with stirring. The progress of reaction was monitored by TLC. The reaction mixture was cooled to 25° C. and filtered through celite; residue was washed with ethyl acetate (2×10 ml). The filtrate was concentrated under reduced pressure to obtain a crude product; which was purified by flash column chromatography using 10% ethyl acetate in hexanes as an eluent to obtain the title compound (0.25 g, 77.0%). MS: m/z 279 (M+1).

Workup

  1. customthe nitrogen gas was bubbled through reaction mixture for 15 minutes
  2. customthe tube was sealed
  3. customThe progress of reaction
  4. temperatureThe reaction mixture was cooled to 25° C.
  5. filtrationfiltered through celite
  6. washresidue was washed with ethyl acetate (2×10 ml)
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customto obtain a crude product
  9. customwhich was purified by flash column chromatography

Sources & evidence

ORD record
ord-091dd04808f44804bb9a3210181a8494
Source dataset
uspto-grants-2016_07
Patent number
US09388196B2

Reaction notes

Loading…