1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 67312258, compound

HRID 1804663Notes

Reaction equation

HRID 1804663 reaction equation
C1CCN2C(=NCCC2)CC1.[CH3:12][O:13][C:14](=[O:38])[NH:15][C@H:16]([C:20]([N:22]1[CH2:26][CH2:25][CH2:24][C@H:23]1[C:27]1[NH:31][C:30]2[CH:32]=[C:33]([C:36]#[CH:37])[CH:34]=[CH:35][C:29]=2[N:28]=1)=[O:21])[CH:17]([CH3:19])[CH3:18].[CH3:39][O:40][C:41](=[O:66])[NH:42][C@H:43]([C:47]([N:49]1[CH2:53][CH2:52][CH2:51][C@H:50]1[C:54]1[NH:58][C:57]2[CH:59]=[C:60]([N:63]=[N+:64]=[N-:65])[CH:61]=[CH:62][C:56]=2[N:55]=1)=[O:48])[CH:44]([CH3:46])[CH3:45]>C1(C)C=CC=CC=1.[Cu]I>[CH3:12][O:13][C:14](=[O:38])[NH:15][C@H:16]([C:20]([N:22]1[CH2:26][CH2:25][CH2:24][C@H:23]1[C:27]1[NH:31][C:30]2[CH:32]=[C:33]([C:36]3[N:65]=[N:64][N:63]([C:60]4[CH:61]=[CH:62][C:56]5[N:55]=[C:54]([C@@H:50]6[CH2:51][CH2:52][CH2:53][N:49]6[C:47](=[O:48])[C@@H:43]([NH:42][C:41]([O:40][CH3:39])=[O:66])[CH:44]([CH3:46])[CH3:45])[NH:58][C:57]=5[CH:59]=4)[CH:37]=3)[CH:34]=[CH:35][C:29]=2[N:28]=1)=[O:21])[CH:17]([CH3:19])[CH3:18]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 59611358HCID 59611358, compoundHCID 86655310HCID 86655310, compound

Product 1

HCID 67312258HCID 67312258, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent3×

Procedure

DBU (154 μL, 1.03 mmol) is diluted in 0.5 mL of anhydrous toluene. Copper(I) iodide (5.9 mg, 0.031 mmol) is added followed by a solution of {(S)-1-[(S)-2-(6-Ethynyl-1H-benzoimidazol-2-yl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester intermediate 14 (38 mg, 0.10 mmol) in 0.5 mL of toluene and a solution of {(S)-1-[(S)-2-(6-Azido-1H-benzoimidazol-2-yl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester intermediate 20 (50 mg, 0.13 mmol) in 1.0 mL of toluene. The resulting mixture is submitted to microwave for 30 minutes at normal power. The final mixture is filtrated through a pad of celite using DCM. The filtrate is concentrated and purified by flash chromatography on silica gel (MeOH/CH2Cl2, 0% to 15%) The compound is further purified by reverse phase HPLC to give title compound (6.5 mg) as a white solid.

Workup

  1. filtrationThe final mixture is filtrated through a pad of celite
  2. concentrationThe filtrate is concentrated
  3. custompurified by flash chromatography on silica gel (MeOH/CH2Cl2, 0% to 15%) The compound
  4. customis further purified by reverse phase HPLC

Sources & evidence

ORD record
ord-fc6b37fbc57d420a8d741a708fbccd4e
Source dataset
uspto-grants-2013_01
Patent number
US08354419B2

Reaction notes

Loading…