1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-(4-Bromo-2-fluoro-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid ethyl ester

HRID 1366773Notes

Reaction equation

HRID 1366773 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:14][C:13]2[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1OS(C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)(=O)=O)=[O:5])[CH3:2].[Br:32][C:33]1[CH:39]=[CH:38][C:36]([NH2:37])=[C:35]([F:40])[CH:34]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C1CCN2C(=NCCC2)CC1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([C:6]1[S:14][C:13]2[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:37][C:36]1[CH:38]=[CH:39][C:33]([Br:32])=[CH:34][C:35]=1[F:40])=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 1230504-Bromo-2-fluoroanilineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 597039083-(Nonafluorobutane-1-sulfonyloxy)-thieno[3,2-c]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 597038743-(4-Bromo-2-fluoro-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 64%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A degassed solution of 3-(nonafluorobutane-1-sulfonyloxy)-thieno[3,2-c]pyridine-2-carboxylic acid ethyl ester (422 mg, 0.83 mmol), 4bromo -2-fluoroaniline (206 mg, 1.08 mmol), Pd2 dba3 (38 mg, 0.04 mmol), Xantphos (48 mg, 0.08 mmol) and DBU (316 μl, 2.08 mmol) in toluene (1 ml) was subjected to microwave irradiation at 150° C. for 10 minutes. The reaction mixture was cooled to ambient temperature then diluted with ethyl acetate (30 ml). The resultant solution was washed with water (20 ml), dried over sodium sulfate and concentrated in vacuo to give a solid residue. The solid residue was purified by flash chromatography (Si-SPE, pentane:diethyl ether, gradient 90:10 to 70:30) to afford the title compound as a white solid (210 mg, 64%). LCMS (method B): RT=3.78 min, M+H+=395/397.

Workup

  1. customirradiation at 150° C. for 10 minutes
  2. washThe resultant solution was washed with water (20 ml)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customto give a solid residue
  6. customThe solid residue was purified by flash chromatography (Si-SPE, pentane:diethyl ether, gradient 90:10 to 70:30)

Sources & evidence

ORD record
ord-543dd4da60c8452d87acf4577df6922c
Source dataset
uspto-grants-2011_02
Patent number
US07893085B2

Reaction notes

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