Pyridine → HCID 66791565, compound

HRID 1096664Notes

Reaction equation

HRID 1096664 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]=[C:5]1[C@@H:13]1[CH2:18][CH2:17][CH2:16][N:15]([C:19](=[O:41])[CH2:20][C@H:21]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=2)[CH2:14]1.ClCCl.[C:45](Cl)(=[O:47])[CH3:46].N1C=CC=CC=1>CO>[C:45]([NH:1][CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]=[C:5]1[C@@H:13]1[CH2:18][CH2:17][CH2:16][N:15]([C:19](=[O:41])[CH2:20][C@H:21]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:38])[CH3:39])[CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=2)[CH2:14]1)(=[O:47])[CH3:46]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 6367Acetyl chlorideHCID 66791601HCID 66791601, compound

Product 1

HCID 66791565HCID 66791565, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl (R)-4-((R)-3-(1-(2-aminoethyl)-1H-benzo[d]imidazoI-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (129D) was added to a 25 mL round-bottomed flask equipped for stirring under nitrogen. Dichloromethane (5 mL) was added and the solution was cooled to 0° C. with an ice/water bath. Acetyl chloride (0.703 mmoles; 0.050 mL) and pyridine (2.47 mmoles, 0.200 mL) were then added and the resultant solution was stirred at 0° C. for 10 min. Solution was allowed to warm to it and stirred for 1 hr. The reaction solution was subsequently concentrated in-vacuo, re-dissolved in methanol (3 mL), and then directly purified by preparative LC/MS (20-90% CH3CN in H2O) to afford tert-butyl (R)-4-((R)-3-(1-(2-acetamidoethyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (129E) as a clear oil (0.038 mmoles, 0.023 g, 36% yield over 2-steps). ESI-MS: m/z 598.5 (M+H)+.

Workup

  1. customequipped
  2. temperatureto warm to it
  3. stirringstirred for 1 hr
  4. customdirectly purified by preparative LC/MS (20-90% CH3CN in H2O)

Sources & evidence

ORD record
ord-0638a26d5a764ee89cf907233507b8f5
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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