Potassium Carbonate → 5-Bromo-3-(1-(2-fluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine

HRID 531464Notes

Reaction equation

HRID 531464 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[CH:9][N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1.[F:22][C:23]1[CH:43]=[CH:42][CH:41]=[CH:40][C:24]=1[CH2:25][N:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.C1(C)C=CC=CC=1.C(O)C.O.C(=O)([O-])[O-].[K+].[K+]>CCCCCC.C(OCC)(=O)C.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>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:29]3[CH:28]=[N:27][N:26]([CH2:25][C:24]4[CH:40]=[CH:41][CH:42]=[CH:43][C:23]=4[F:22])[CH:30]=3)=[CH:9][N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 497590665-bromo-3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 86587398Ethanol toluene waterHCID 867218291-[(2-Fluorophenyl)methyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 718182675-Bromo-3-(1-(2-fluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineYield 65.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

5-Bromo-3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine (Intermediate-1) (350 mg, 0.83 mmol) and 1-(2-fluorobenzyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (Intermediate-2) (301 mg, 0.99 mmol) were added to a solution of toluene/ethanol/water (5/5/2.5 ml) previously purged with argon (10 min). The reaction mixture was purged with argon for a further 15 mins, followed by the addition of potassium carbonate (230 mg, 1.6 mmol) and Pd(PPh3)4 (48 mg, 0.0415 mmol). The resulting mixture was heated to reflux at 80° C. overnight. The reaction was monitored by TLC (50% ethylacetate in hexane). The reaction mixture was cooled and diluted with ethyl acetate (50 ml) and washed with water (2×50 ml). The organic layer was dried over Na2SO4, and concentrated under reduced pressure to afford crude product. Purification by column chromatography on silica gel (20% ethyl acetate in hexane) afforded 285 mg (43.64% yield) of titled compound. MS: m/z=527.0 (M+1).

Workup

  1. custompreviously purged with argon (10 min)
  2. customThe reaction mixture was purged with argon for a further 15 mins
  3. temperatureThe resulting mixture was heated
  4. temperatureThe reaction mixture was cooled
  5. washwashed with water (2×50 ml)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude product
  9. customPurification by column chromatography on silica gel (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-2fa4e811a2db437aae4bc8e991cfad34
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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