Lithium Chloride → (1s,2s,4s)-2-Methoxy-4-[4-(4-methyl-thiazol-2-yl)-2-trifluoromethyl-benzenesulfonyl]-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide

HRID 1367482Notes

Reaction equation

HRID 1367482 reaction equation
[C:1]([C:3]1([NH:6][C:7]([C@H:9]2[CH2:13][C@H:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20](Br)=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])(=[O:16])=[O:15])[CH2:11][C@@H:10]2[O:28][CH3:29])=[O:8])[CH2:5][CH2:4]1)#[N:2].[CH3:30][C:31]1[N:32]=[C:33]([Sn](CCCC)(CCCC)CCCC)[S:34][CH:35]=1.[Li+].[Cl-]>O1CCOCC1.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>[C:1]([C:3]1([NH:6][C:7]([C@H:9]2[CH2:13][C@H:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20]([C:33]4[S:34][CH:35]=[C:31]([CH3:30])[N:32]=4)=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])(=[O:16])=[O:15])[CH2:11][C@@H:10]2[O:28][CH3:29])=[O:8])[CH2:5][CH2:4]1)#[N:2]

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 164271304-Methyl-2-(tributylstannyl)-1,3-thiazoleHCID 59619475(1S,2S,4S)-4-(4-Bromo-2-trifluoromethyl-benzenesulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide

Product 1

HCID 59619226(1s,2s,4s)-2-Methoxy-4-[4-(4-methyl-thiazol-2-yl)-2-trifluoromethyl-benzenesulfonyl]-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amideYield 36.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a suspension of (1R,2R,4R) and (1S,2S,4S)-4-(4-bromo-2-trifluoromethyl-benzenesulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide (40 mg, 0.0808 mmol, example 58) in dioxane (1.5 ml) was added a solution of 4-methyl-2-(tributylstannyl)-thiazole (38 mg, 0.0970 mmol) in dioxane (0.5 ml) and argon was bubbled through the resulting mixture for 10 minutes. Then LiCl (10 mg, 0.242 mmol) and tetrakis(triphenylphosphine)palladium(0) (5 mg, 0.00404 mmol) were added and the mixture was stirred at reflux for 3.5 h. The reaction mixture was allowed to cool to room temperature, diluted with DCM and filtered through a pad of silica gel. The filtrate was evaporated and the remaining light brown solid was purified by silica column chromatography (DCM/EtOAc 4:1) to obtain a white solid (15 mg) which was triturated with ether to obtain the title compound (9 mg, 22%) as a white solid.

Workup

  1. customwas bubbled through the resulting mixture for 10 minutes
  2. temperatureat reflux for 3.5 h
  3. filtrationfiltered through a pad of silica gel
  4. customThe filtrate was evaporated
  5. customthe remaining light brown solid was purified by silica column chromatography (DCM/EtOAc 4:1)

Sources & evidence

ORD record
ord-1a1d38b5f34a42169ee5f2945585420b
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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