Lithium Chloride → HCID 58209539, compound

HRID 1919185Notes

Reaction equation

HRID 1919185 reaction equation
[CH2:1]([Sn](CCCC)(CCCC)C#C)[CH2:2]CC.Br[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:24]=[C:25]([C@@H:28]3[CH2:32][CH2:31][CH2:30][N:29]3[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[NH:26][CH:27]=2)=[CH:19][CH:18]=1.[Li+].[Cl-]>O1CCOCC1.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:17]1[CH:22]=[CH:21][C:20]([C:23]2[NH:24][C:25]([C@@H:28]3[CH2:32][CH2:31][CH2:30][N:29]3[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[N:26][CH:27]=2)=[CH:19][CH:18]=1)#[CH:2]

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 621176EthynyltributyltinHCID 178451912HCID 178451912, compound

Product 1

HCID 58209539HCID 58209539, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Pd(Ph3P)4 (0.115 g, 0.099 mmol) was added to a mixture of tributyl(ethynyl)stannane (1.539 g, 4.88 mmol), (S)-tert-butyl 2-(4-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (0.965 g, 2.46 mmol; for its preparation, see PCT Publication No. WO 2008/021927) and LiCl (0.277 g, 6.53 mmol) in dioxane (20 mL) in a sealed pressure tube. The mixture was purged with nitrogen, sealed and heated at 80° C. for 3 hr. After it was allowed to cool to ambient temperature, the volatile component was removed in vacuo and the residue was partitioned between CH3CN and hexanes (2:1 ratio in volume). The hexane layer was washed with an equal volume of CH3CN. The combined CH3CN phase was rotervaped, and the resultant crude material was purified with a BIOTAGE® (100 g silica gel; 40-50% EtOAc/hexanes) to afford Intermediate M1a as a dull orange solid (591 mg). 1H NMR (DMSO-d6, δ=2.50 ppm, 400 MHz): 12.21/11.95/11.88 (three ‘br s’, 1H), 7.74 (d, J=8.3, 1.6H), 7.66-7.47 (m, 1.66H), 7.41 (d, J=8.3, 1.6H), 7.32 (m, 0.14H), 4.84-4.75 (m, 1H), 4.19/4.12 (two ‘s’, 1H), 3.52 (m, 1H), 3.39-3.29 (m, 1H), 2.28-1.77 (m, 4H), 1.39/1.15 (two ‘s’, 9H). LC/MS: Anal. Calcd. for (M+H)+ C20H24N3O2: 338.18. Found, 338.28.

Workup

  1. customfor its preparation
  2. customThe mixture was purged with nitrogen
  3. customsealed
  4. temperatureto cool to ambient temperature
  5. customthe volatile component was removed in vacuo
  6. customthe residue was partitioned between CH3CN and hexanes (2:1 ratio in volume)
  7. washThe hexane layer was washed with an equal volume of CH3CN
  8. customthe resultant crude material was purified with a BIOTAGE® (100 g silica gel; 40-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-321b17ac0382405d86bf569e04712765
Source dataset
uspto-grants-2013_12
Patent number
US08618153B2

Reaction notes

Loading…