Azetidine → HCID 44177925, compound

HRID 1673040Notes

Reaction equation

HRID 1673040 reaction equation
Br[C:2]1[N:3]=[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]([F:32])([F:31])[F:30])[N:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([CH3:22])(=[O:21])=[O:20])[CH:14]=3)=[CH:9][CH:8]=2)[CH:6]=1.[NH:33]1[CH2:36][CH2:35][CH2:34]1.N1CCC[C@H]1C(O)=O.[C:45]([O-:48])([O-])=[O:46].[Cs+].[Cs+]>[Cu]I.CN(C=O)C>[C:45]([OH:48])([C:29]([F:32])([F:31])[F:30])=[O:46].[N:33]1([C:2]2[N:3]=[C:4]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]([F:31])([F:30])[F:32])[N:5]([C:7]3[CH:8]=[CH:9][C:10]([C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([CH3:22])(=[O:21])=[O:20])[CH:14]=4)=[CH:11][CH:12]=3)[CH:6]=2)[CH2:36][CH2:35][CH2:34]1

Participants

8

Reactant 4

HCID 10422AzetidineHCID 10796Cesium carbonateHCID 145742L-ProlineHCID 59240043HCID 59240043, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 44177925HCID 44177925, compoundYield 52.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

4-bromo-1-(3′-(methylsulfonyl)biphenyl-4-yl)-2-(2-(trifluoromethyl)phenyl)-1H-imidazole (188 mgs, 0.361 mmol), azetidine (0.4 mL 5.94 mmol), L-proline (50 mg, 0.434 mmol), Cs2CO3 (517 mg, 1.44 mmol), 2.5 mL anhydrous DMF, and CuI (69 mg, 362 mmol) were added to a 5 mL microwave tube and sealed. The tube was purged with an argon balloon for five minutes. The reaction was heated at 120° C. for 24 h and then cooled to room temperature. The crude reaction mixture was purified directly by HPLC using water: TFA: acetonitrile as eluents to afford 4-(azetidin-1-yl)-1-(3′-(methylsulfonyl)biphenyl-4-yl)-2-(2-(trifluoromethyl)phenyl)-1H-imidazole (47 mgs, 26%) as a light yellow solid. 1H-NMR (DMSO, 400 MHz) δ 8.12-8.11 (m, 1H), 8.02-7.99 (m, 1H), 7.91-7.88 (m, 1H), 7.82-7.80 (m, 1H), 7.76 (d, J=8.60 Hz, 2H), 7.73-7.69 (m, 1H), 7.65-7.62 (m, 2H), 7.46-7.44 (m, 1H), 7.23 (d, J=8.60 Hz, 2H), 6.77 (s, 1H), 3.74 (t, J=7.34 Hz, 4H), 3.28 (s, 3H), 2.33-2.25 (m, 2H); MS (ES): 498.3 [M+H]+.

Workup

  1. customsealed
  2. customThe tube was purged with an argon balloon for five minutes
  3. temperaturecooled to room temperature
  4. customThe crude reaction mixture
  5. customwas purified directly by HPLC

Sources & evidence

ORD record
ord-4727ff470b1945099fc9d9cf72cfb966
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

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