Sodium Carbonate → 1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid {(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-yl}-amide

HRID 2046573Notes

Reaction equation

HRID 2046573 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[C@@H:14]([NH:18][C:19]([C:21]2([NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])[CH2:23][CH2:22]2)=[O:20])[CH2:13][CH2:12]3)O1.Br[C:33]1[CH:38]=[C:37]([Cl:39])[CH:36]=[C:35]([F:40])[C:34]=1[C:41]1[N:45]=[C:44]([CH3:46])[O:43][N:42]=1.C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O.O.[Pd](Cl)Cl>[Cl:39][C:37]1[CH:36]=[C:35]([F:40])[C:34]([C:41]2[N:45]=[C:44]([CH3:46])[O:43][N:42]=2)=[C:33]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[C@@H:14]([NH:18][C:19]([C:21]2([NH:24][C:25](=[O:30])[C:26]([F:28])([F:29])[F:27])[CH2:23][CH2:22]2)=[O:20])[CH2:13][CH2:12]3)[CH:38]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 684506413-(2-Bromo-4-chloro-6-fluorophenyl)-5-methyl-1,2,4-oxadiazoleHCID 866757751-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid [(S)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yl]-amide

Product 1

HCID 601420281-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid {(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-yl}-amideYield 54.3%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid[(S)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yl]-amide (intermediate A-2) (0.145 g, 331 μmol) and 3-(2-bromo-4-chloro-6-fluoro-phenyl)-5-methyl-[1,2,4]oxadiazole (intermediate B-2) (106 mg, 364 μmol) were dissolved in DMSO (5.00 ml), then sodium carbonate (87.7 mg, 827 μmol), dissolved in water (0.63 ml) was added, followed by (1,1′-bis-diphenylphosphino)-ferrocene)palladium-(II)dichloride (1:1 complex with CH2Cl2) (12.1 mg, 16.5 μmol, eq: 0.05). This mixture was heated up to 80° C. for 2 hours, then poured into H2O (50 ml) and extracted with CH2Cl2 (2×25 mL). The organic layers were dried over MgSO4, filtered and concentrated in vacuo to give a crude product (0.213 g) which was purified by flash chromatography (silica gel, 20 g, 10% to 50% EtOAc in heptane) to yield the title compound (0.094 g, 54%) as light yellow solid. MS: 523.1 (MH+, 1Cl).

Workup

  1. additionwas added
  2. extractionextracted with CH2Cl2 (2×25 mL)
  3. dry with materialThe organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a crude product (0.213 g) which
  7. customwas purified by flash chromatography (silica gel, 20 g, 10% to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-5c05e79ba16f4ef39649cdc22d61e361
Source dataset
uspto-grants-2013_11
Patent number
US08592426B2

Reaction notes

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