Dichloromethane → 9-Cyclopentyl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

HRID 1190454Notes

Reaction equation

HRID 1190454 reaction equation
C(Cl)Cl.Br[C:5]1[CH:6]=[CH:7][C:8]2[O:17][CH2:16][CH2:15][C:14]3[S:13][C:12]([C:18]4[N:19]([CH:23]([CH3:25])[CH3:24])[N:20]=[CH:21][N:22]=4)=[N:11][C:10]=3[C:9]=2[CH:26]=1.[Br-].[CH:28]1([Zn+])[CH2:32][CH2:31][CH2:30][CH2:29]1>CC(N(C)C)=O.CCOC(C)=O.Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Cu]I>[CH:28]1([C:5]2[CH:6]=[CH:7][C:8]3[O:17][CH2:16][CH2:15][C:14]4[S:13][C:12]([C:18]5[N:19]([CH:23]([CH3:25])[CH3:24])[N:20]=[CH:21][N:22]=5)=[N:11][C:10]=4[C:9]=3[CH:26]=2)[CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

9

Reactant 3

HCID 6344DichloromethaneHCID 532349749-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azuleneHCID 178419768HCID 178419768, compound

Product 1

HCID 582037209-Cyclopentyl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azuleneYield 10%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with DCM (1:1) (8.45 mg, 0.0104 mmol), copper(I) iodide (3.94 mg, 0.0207 mmol) and 9-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene from Example 6 (0.081 g, 0.21 mmol) were mixed in DMA (2.5 mL) and stirred under argon for 10 min and cyclopentylzinc bromide (0.5 M in THF, 0.42 mL, 0.21 mmol) was transferred to this mixture via syringe. The reaction was carried out at 80° C. Subsequently cooled to room temp. and diluted with EtOAc and 1 N HCl and worked up. Purified via rp-HPLC to provide 251 (8 mg, 10% yield). LC/MS (ESI+): m/z 381 (M+H). 1H NMR (400 MHz, DMSO) δ 8.27 (d, J=2.0, 1H), 8.08 (d, J=16.1, 1H), 7.16 (dd, J=8.2, 2.1, 1H), 6.98 (d, J=8.2, 1H), 5.83 (dt, J=13.2, 6.7, 1H), 4.34 (t, J=5.0, 2H), 3.42 (t, J=5.0, 2H), 3.05 (p, J=8.3, 1H), 2.19-1.98 (m, 2H), 1.73 (ddd, J=11.4, 6.9, 3.8, 4H), 1.61-1.48 (m, 8H).

Workup

  1. customwas carried out at 80° C
  2. temperatureSubsequently cooled to room temp.
  3. customPurified via rp-HPLC

Sources & evidence

ORD record
ord-b7d41ff6f7244d07af4705d910f7c63e
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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