Hydrazine → HCID 135983722, compound

HRID 603051Notes

Reaction equation

HRID 603051 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([CH2:11][C:12](=O)[CH2:13][N:14](C)C)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH2:18]N.[OH:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+]>CCO.O.CO.Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C>[N:14]1[NH:18][C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:25]4[CH:26]=[C:21]([OH:20])[CH:22]=[CH:23][CH:24]=4)[CH:3]=3)[NH:8][CH:9]=2)=[CH:12][CH:13]=1

Participants

10

Reactant 4

HCID 9321HydrazineHCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 67061208HCID 67061208, compound

Product 1

HCID 135983722HCID 135983722, compoundYield 34.1%

Reagents, catalysts & solvents 5

HCID 178418903HCID 178418903, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 1-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-yl)-3-dimethylamino-propanone (30 mg, 0.102 mmol) in EtOH was added hydrazine (5 uL, 0.122 mmol). The reaction mixture was stirred at 80° C. for 3 h, then concentrated in vacuo. To the crude was added 3-hydroxyphenyl boronic acid (18 mg, 0.1.32 mmol) and dichlorobis (triphenylphosphino)palladium (ii) (4 mg, 0.006 mmol), and 1 mL of a 1:1 mixture of acetonitrile, and a 2 M solution of sodium carbonate in water. The reaction was run in a Personal Chemistry® microwave reactor at 150° C. for 600 s. The reaction mixture was diluted with methanol (ca. 6 mL), filtered, and the filtrate was adsorbed on silica gel. Purification on silica gel with a gradient of MeOH/CH2Cl2 afforded a beige solid that was further purified by reverse phase chromatography using a gradient of H2O and acetonitrile (with 0.1% formic acid as a modifier) to give 3-[3-(2H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-phenol as white solid (9.6 mg, 34% yield). 1H NMR (500 MHz, DMSO-d6) δ 6.61 (d, J=2.0 Hz, 1H), 6.71 (dd, J=2.5, 8.0 Hz, 1H), 7.03 (s, 1H), 7.08 (d, J=8.0 Hz, 1H), 7.22 (t, J=8.0 Hz, 1H), 7.65 (broad s, 1H), 7.84 (d, J=2.5 Hz, 1H), 8.43 (d, J=2.0 Hz, 1H), 8.53 (broad s, 1H), 9.51 (broad s, 1H), 11.8 (broad s, 1H). MS: m/z 277 (M+H+).

Workup

  1. concentrationconcentrated in vacuo
  2. additionTo the crude was added
  3. waitThe reaction was run in a Personal Chemistry® microwave reactor at 150° C. for 600 s
  4. filtrationfiltered
  5. customPurification on silica gel with a gradient of MeOH/CH2Cl2
  6. customafforded a beige solid
  7. customthat was further purified by reverse phase chromatography

Sources & evidence

ORD record
ord-0403e1e9972649f4adb4756ce52cf23f
Source dataset
uspto-grants-2011_03
Patent number
US07906648B2

Reaction notes

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