Acetic Acid → HCID 58095126, compound

HRID 2282323Notes

Reaction equation

HRID 2282323 reaction equation
C([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:13][C:12]([C:14]2[C:15]([CH3:23])=[N:16][N:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=23)=[CH:11][C:10]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[Cl:31])C=C.C(O)(=O)C.C1([SiH3])C=CC=CC=1>C(Cl)Cl.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>[Cl:31][C:25]1[CH:26]=[C:27]([Cl:30])[CH:28]=[CH:29][C:24]=1[C:10]1[CH:11]=[C:12]([C:14]2[C:15]([CH3:23])=[N:16][N:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=23)[S:13][C:9]=1[C:5]1[NH:4][CH:8]=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 12752PhenylsilaneHCID 66855938HCID 66855938, compound

Product 1

HCID 58095126HCID 58095126, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 1-allyl-2-[3-(2,4-dichlorophenyl)-5-(tributylstannyl)-2-thienyl]-1H-imidazole (180 mg, 0.29 mmol) in DMF (4.0 mL) was added [3-bromo-2-methylpyrazolo[1,5-a]pyridine (50 mg, 0.2 mmol) (azeotroped from toluene) and Bis(triphenylphosphine)palladium(II) chloride (8.5 mg, 0.012 mmol). The resulting mixture was degassed and stirred for 1 h at 100° C. under an atmosphere of argon. The reaction mixture was allowed to cool, concentrated and the residue was partially purified by silica gel column chromatography (40 g, eluting with 30% EtOAc in hexanes to EtOAc to give 3-[5-(1-allyl-1H-imidazol-2-yl)-4-(2,4-dichlorophenyl)-2-thienyl]-2-methylpyrazolo[1,5-a]pyridine, 82 mg. To a solution of [A] 3-[5-(1-allyl-1H-imidazol-2-yl)-4-(2,4-dichlorophenyl)-2-thienyl]-2-methylpyrazolo[1,5-a]pyridine (70 mg, 0.2 mmol), tetrakis(triphenylphosphine)palladium(0) (8.5 mg, 0.0074 mmol) and acetic acid (0.4 mL, 7 mmol) in DCM (1.5 mL) was added slowly phenylsilane (0.1 mL, 0.8 mmol) and the reaction mixture stirred at 40° C. for 2 h. The reaction mixture was concentrated and the product was purified by column chromatography on silica gel eluting with 1-3% MeOH in DCM. The product was further purified by preparative hplc, formic acid gradient. The title compound was isolated as a colorless lyophilized solid, 25 mg. LC/MS (FA) ES+ 425.0, 427.6, 428.4, 429.3. 1H NMR (400 MHz, d4-MeOH) δ: 8.48 (d, J=8.3 Hz, 1H), 7.85-7.87 (m, 1H), 7.50-7.60 (m, 1H), 7.31-7.39 (m, 3H), 7.18 (s, 1H), 7.04 (s, 2H), 6.90-6.95 (m, 1H), 2.62 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe product was purified by column chromatography on silica gel eluting with 1-3% MeOH in DCM
  3. customThe product was further purified by preparative hplc, formic acid gradient

Sources & evidence

ORD record
ord-8f4c6f89677d4b0c80c814c01f219940
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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