1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ammonium Hydroxide

HRID 1716587Notes

Reaction equation

HRID 1716587 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][C@H:6]([C:11](O)=[O:12])[CH2:5]2.CC[N:16]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH3:35][O:36][C@H:37]1[C@H:42]([N:43]2[C:47]3[CH:48]=[CH:49][C:50]([CH3:52])=[CH:51][C:46]=3[N:45]=[C:44]2[CH3:53])[CH2:41][CH2:40][NH:39][CH2:38]1>C(Cl)Cl>[NH4+:16].[OH-:12].[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][C@H:6]([CH2:11][N:39]1[CH2:40][CH2:41][C@@H:42]([N:43]3[C:47]4[CH:48]=[CH:49][C:50]([CH3:52])=[CH:51][C:46]=4[N:45]=[C:44]3[CH3:53])[C@H:37]([O:36][CH3:35])[CH2:38]1)[CH2:5]2

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 18391224HCID 18391224, compoundHCID 68509047HCID 68509047, compound

Product 2

HCID 14923Ammonium HydroxideYield 1%HCID 44455414HCID 44455414, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a flask equipped with a magnetic stir bar and addition funnel under argon atmosphere was added (S)-5-bromo-indan-2-carboxylic acid (383 mg, 1.59 mmol, obtained by following the procedures of patent WO96/23760), EDCI (358 mg, 1.87 mmol), HOBT (291 mg, 2.16 mmol) and CH2Cl2 (3 mL). This solution was stirred at rt for 5 min. To this solution was then added dropwise a solution of (3R,4R)-1-(3-methoxy-piperidin-4-yl)-2,5-dimethyl-1H-benzoimidazole (375 mg, 1.44 mmol) in CH2Cl2 (2 mL). The reaction was then stirred at rt overnight for 20 hours. The reaction was quenched by the addition of water (10 mL) and extracted three times with CH2Cl2. The organic extracts were combined and dried over Na2SO4, filtered and concentrated in vacuo. Flash chromatography (Biotage 12M column, 3% CH3OH in ethyl acetate plus 1% NH4OH) afforded the desired product which was contaminated with some HOBT. The product foam was then dissolved in CH2Cl2 and washed with a saturated NaHCO3 solution. The organic was dried over Na2SO4, filtered and concentrated under reduced pressure to yield ((S)-5-bromo-indan-2-yl)-[(3R,4R)-4-(2,5-dimethyl-benzoimidazol-1-yl)-3-methoxy-piperidin-1-yl]-methanone (579 mg, 83%) as a light yellow foam. HR-ES(+) m/e calcd for C25H28N3O2Br (M+H)+ 482.1438, found 482.1436.

Workup

  1. customTo a flask equipped with a magnetic stir bar and addition funnel under argon atmosphere
  2. customobtained
  3. stirringThe reaction was then stirred at rt overnight for 20 hours
  4. customThe reaction was quenched by the addition of water (10 mL)
  5. extractionextracted three times with CH2Cl2
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-be5ea8be59ab454aac42561de48bdba3
Source dataset
uspto-grants-2010_09
Patent number
US07803816B2

Reaction notes

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