1,8-Diazabicyclo(5.4.0)undec-7-ene → Ethyl 3-(4-bromo-2-fluoro-phenylamino)-thieno[2,3-c]pyridine-2-carboxylate

HRID 1366782Notes

Reaction equation

HRID 1366782 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:14][C:9]2=[CH:10][N:11]=[CH:12][CH:13]=[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:9]2=[CH:10][N:11]=[CH:12][CH:13]=[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 597039143-(Nonafluorobutane-1-sulfonyloxy)-thieno[2,3-c]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 59703899Ethyl 3-(4-bromo-2-fluoro-phenylamino)-thieno[2,3-c]pyridine-2-carboxylateYield 67.2%

Reagents, catalysts & solvents 3

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

Procedure

A degassed solution of 3-(nonafluorobutane-1-sulfonyloxy)-thieno[2,3-c]pyridine-2-carboxylic acid ethyl ester (678 mg, 1.33 mmol), 4bromo -2-fluoroaniline (329 mg, 1.73 mmol), Pd2 dba3 (61 mg, 0.07 mmol), Xantphos (78 mg, 0.14 mmol) and DBU (509 μl, 3.35 mmol) in toluene (3 ml) was subjected to mnicrowave irradiation at 150° C. for 10 minutes. The reaction mixture was cooled to ambient temperature then diluted with ethyl acetate (70 ml). The resultant solution was washed with water (20 ml), dried over sodium sulfate and concentrated in vacuo to give an orange oil. The oil was purified by flash chromatography (Si-SPE, pentane:diethyl ether, gradient 90:10 to 50:50) followed by crystallisation from ethyl acetate:pentane to provide the title compound as a white solid (353 mg, 67%). LCMS (method B): RT=4.08 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 an orange oil
  6. customThe oil was purified by flash chromatography (Si-SPE, pentane:diethyl ether, gradient 90:10 to 50:50)
  7. customfollowed by crystallisation from ethyl acetate

Sources & evidence

ORD record
ord-57cef48e8c9344f7a0f4f6d967f494d2
Source dataset
uspto-grants-2011_02
Patent number
US07893085B2

Reaction notes

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