Hydrochloric Acid → HCID 86643482, compound

HRID 1423370Notes

Reaction equation

HRID 1423370 reaction equation
[Br:1][C:2]1[C:15]([O:16][CH3:17])=[CH:14][C:13]2[C:4](=[C:5]([O:20][C@H:21]3[CH2:25][N:24](C(OC(C)(C)C)=O)[C@H:23]([C:33]([O:35][CH3:36])=[O:34])[CH2:22]3)[N:6]=[C:7]3[C:12]=2[CH:11]=[CH:10][C:9]([C:18]#[N:19])=[CH:8]3)[CH:3]=1.[ClH:37]>C(Cl)Cl>[ClH:37].[Br:1][C:2]1[C:15]([O:16][CH3:17])=[CH:14][C:13]2[C:4](=[C:5]([O:20][C@H:21]3[CH2:25][NH:24][C@H:23]([C:33]([O:35][CH3:36])=[O:34])[CH2:22]3)[N:6]=[C:7]3[C:12]=2[CH:11]=[CH:10][C:9]([C:18]#[N:19])=[CH:8]3)[CH:3]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 59408872HCID 59408872, compound2×

Product 1

HCID 86643482HCID 86643482, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product mixture from Step 1, 1-tert-butyl 2-methyl (2S,4R)-4-[(8-bromo-3-cyano-9-methoxyphenanthridin-6-yl)oxy]pyrrolidine-1,2-dicarboxylate (419 mg, 0.75 mmol) in DCM (10 mL) was bubbled HCl(g) for 20 min. After stirring for an additional 30 min, the solvent was removed in vacuo to yield methyl (4R)-4-[(8-bromo-3-cyano-9-methoxyphenanthridin-6-yl)oxy]-L-prolinate hydrochloride, which was taken up in DCM (5 mL) and linker intermediate B21, (2S)-cyclopentyl({[(2,2-dimethylpent-4-en-1-yl)oxy]carbonyl}amino)acetic acid (234 mg, 0.83 mmol), TEA (0.314 mL, 2.25 mmol), EDC (187 mg, 0.98 mmol), and HOBT (149 mg, 0.98 mmol) were added. The mixture was stirred at r.t. for 18 h, the solvent was removed in vacuo, and the residue was taken up in EtOAc and extracted with NaHCO3. The organic layer was dried over MgSO4 and the solvent was removed in vacuo. The crude material was then purified on silica (gradient elution, 0-10% EtOAc/MeOH/NH3) to yield the title compound. LRMS (M+H)+=721.4.

Workup

  1. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-0ef8166238a0482488c85d388d41df1b
Source dataset
uspto-grants-2015_01
Patent number
US08927569B2

Reaction notes

Loading…