Diisopropylethylamine → HCID 59837474, compound

HRID 272933Notes

Reaction equation

HRID 272933 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2([C:18]#[N:19])[CH2:17][CH2:16]C[CH2:14][CH2:13]2)=[CH:8][CH:7]=1.ClCCC[O:24]C1C=CC(C2(C#N)CCCCC2)=CC=1.[CH:39]([N:42](CC)[CH:43]([CH3:45])[CH3:44])([CH3:41])[CH3:40].C[C@@H]1CC[C@H](C)N1>CN1C(=O)CCC1>[CH3:45][C@@H:43]1[CH2:44][CH2:41][C@H:39]([CH3:40])[N:42]1[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2([C:18]#[N:19])[CH2:13][CH2:14][O:24][CH2:16][CH2:17]2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5324511(2S)-2β,5α-DimethylpyrrolidineHCID 23091704HCID 23091704, compoundHCID 598375041-[4-(3-Bromo-propoxy)-phenyl]-cyclohexanecarbonitrile

Product 1

HCID 59837474HCID 59837474, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

A (1:3) mixture of 1-[4-(3-bromo-propoxy)-phenyl]-cyclohexanecarbonitrile and 1-[4-(3-chloro-propoxy)-phenyl]-cyclohexanecarbonitrile (150 mg, 0.54 mmol), N,N-diisopropylethylamine (187 μL, 1.07 mmol) and (2R,5S)-2,5-dimethylpyrrolidine (145 mg, 1.07 mmol) in NMP (0.5 mL) was heated at 160° C. in the microwave (Smith Personal Synthesiser) for 400 seconds then 170° C. for 600 seconds. The reaction mixture was quenched with NaHCO3 (15 mL) and extracted with ethyl acetate (2×15 mL), dried over Na2SO4, filtered and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 97:3:0.3 to 90:10:1. Yield=28% 1H NMR (400 MHz, CDCl3) δ7.36 (d, 2H), 6.92 (d, 2H), 4.10-4.04 (m, 2H), 4.00 (t, 2H), 3.88 (dt, 2H), 2.72 (t, 2H), 2.64-2.52 (m, 2H), 2.14-1.98 (m, 4H), 1.94 (pentet, 2H), 1.86-1.78 (m, 2H), 1.42-1.28 (m, 2H), 1.10 (d, 6H); HRMS (ESI+) 343.2380 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with NaHCO3 (15 mL)
  2. extractionextracted with ethyl acetate (2×15 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe compound was purified by column chromatography on Biotage® silica gel
  7. washeluting with dichloromethane

Sources & evidence

ORD record
ord-c53349d7cebb48d5a8beae03db991b2f
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

Loading…