3-Bromoaniline → HCID 68870046, compound

HRID 1782105Notes

Reaction equation

HRID 1782105 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[CH:13]=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[NH:15][C:11]=3[N:10]=[CH:9]2)[CH:5]=[CH:6][CH:7]=1.BrC1C=C(C=CC=1)N.[S:29]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30]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>[S:29]1[CH:33]=[CH:32][C:31]([C:2]2[CH:3]=[C:4]([N:8]3[C:12]4[CH:13]=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[NH:15][C:11]=4[N:10]=[CH:9]3)[CH:5]=[CH:6][CH:7]=2)=[CH:30]1

Participants

5

Reactant 3

HCID 115623-BromoanilineHCID 581760Thiophene-3-boronic acidHCID 68872357HCID 68872357, compound

Product 1

HCID 68870046HCID 68870046, compoundYield 97.5%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

A flask containing a mixture of ethyl 1-(3-bromophenyl)-1,4-dihydropyrrolo[2,3-d]imidazole-5-carboxylate (334 mg, 1 mmol, prepared according to the procedure described for example 1 except using 3-bromoaniline in the first step) and 3-thiophene boronic acid (256 mg, 2 mmol) was degassed and placed under a nitrogen atmosphere To this was quickly added tetrakis(triphenylphosphine)palladium(0) (173.3 mg, 0.15 mmol) in one portion followed by degassed solutions of 1,4-dioxane (5 mL) and aqueous sodium carbonate (2 M, 3 mL). The reaction mixture was heated at 85° C. under nitrogen for 24 hours after which time it was cooled, filtered and concentrated in vacuo. The resulting crude material was chromatographed over silica gel eluting with MeOH:CH2Cl2 0%→2%] to afford 329 mg (97.5%) of ethyl 1-(3-thien-3-ylphenyl)-1,4-dihydropyrrolo[2,3-d]imidazole-5-carboxylate. 1H NMR (400 MHz, CDCl3): δ=8.02 (s, 1H), 7.75-7.72 (m, 1H), 7.58-7.53 (m, 3H), 7.48-7.41 (m, 3H), 6.98 (d, J=1.2 Hz, 1H), 4.37 (q, J=7.2 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H). MS (ES+): m/z 338.13 (100) [MH+].

Workup

  1. additionA flask containing
  2. customprepared
  3. customwas degassed
  4. customby degassed solutions of 1,4-dioxane (5 mL) and aqueous sodium carbonate (2 M, 3 mL)
  5. temperaturewas cooled
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude material was chromatographed over silica gel eluting with MeOH

Sources & evidence

ORD record
ord-635c09f7414c468697d9ae4969cf7673
Source dataset
uspto-grants-2009_03
Patent number
US07498354B2

Reaction notes

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