1-Methylimidazole → HCID 69540464, compound

Participants

Reaction Steps

The new linker based solid support 1 (1.0 g) having substitution 0.4 meq/g was placed in reaction vessel and allowed to swell in dichloromethane (DCM) under nitrogen stirring. After 30 min. the resin was filtered and washed with DCM. To this resin a solution of Boc-Leu (0.45 g, 2 mmol) dimethylaminopyridine (DMAP) or N-methyl imidazole (NMI) (0.4 mmol) in DCM:DMF (1:1) 20 ml and was added. The reaction mixture was stirred for 8-10 hrs. The resin was washed three times with DCM and dried. An aliquot of this dried resin (2.5 mg) was tested for the loading and the loading was found to be 82% [Method B]. The resin was treated with 50% TFA in DCM for 30 min. to remove Boc group. After 30 min the resin was filtered and washed with DCM 20 ml×3, 20% DIEA in DCM 20 ml×3, DCM 20 ml×3 and finally suspended in 20% piperidine solution DMF:DCM (1:1) 20 ml and treated with DCM:DMF (1:1) 20 ml. The resin having free amino group of Leu, was reacted with a solution of Boc-Cys-(Trt) (0.56 g, 1 mmol) and HOBt (0.153 g, 1 mmol) in DCM:DMF (1:1) 20 ml under nitrogen stirring. To this suspension DIC (0.18 ml, 1.2 mmol) was added and the mixture was stirred for 3 hrs until the resin was negative to Kaiser test. It was filtered and washed with DCM:DMF (1:1) 15 ml×3 and finally with DCM. The resin was treated with 50% trifluoroacetic acid (TFA)/Bu3SiH in DCM for 30 min and then washed with 10% trifluoric acid (TFA)/Bu3SiH in DCM for 10 min (three times) to remove both Boc and trytyl group of Cys. After washing the resin with DCM 3 times, a solution of p-anisaldehyde (0.5 ml) in DCM:DMF (1:1) 10 ml was added under stirring. The stirring was continued for 8-10 hrs. The resin was washed three times with DCM. To this resin, a solution of Benzoyl chloride (0.2 ml, 2 mmol) and DIEA (0.4 ml, 2.0 mmol) in DCM:DMF (1:1) 10 ml were added and the stirring were continued for three hrs. After three hours, the resin was negative to Kaiser test. The resin was washed with DCM:DMF (1:1) 10 ml×3, with DMF 10 ml×3, DCM:DMF (1:1) 10 ml×2 and finally three times with DCM and dried. It was treated with a mixture of dioxan-MeOH-4N. NaOH (30:9:1, 20 ml) for 30 min under stirring and the resin was filtered and washed with 2 ml of water. The combined filtrate was evaporated in vacuo. The residue was taken in water and extracted with ether. The aqueous layer acidified with 1N hydrochloric acid to pH 2.0 and extracted with EtOAc (3×70 ml). The combined EtOAc layer was washed with water and brine then dried over Na2SO4 and evaporated in vacuo to yield N-Boc-2-(4-methoxyphenyl)thiazolidinyl-leucine as a glassy material. Yield: 0.11 g, 78%; FAB-MS [M+H]+ 453; 1H NMR (DMSO-d6) δ: 0.9 (m, 6H), 1.2 (bs, 9H), 1.7 (m, 2H), 4.3 (m 1H), 3.5 (m, 2H), 3.7 (s, 3H), 4.86 (bs, 1H), 5.9 (bs, 1H), 6.8-7.1 (Abq, 4H).

Provenance & Evidence