Diisopropylethylamine → 2-(Benzo[1,3]dioxol-5-yloxy)-N-[4-(1-carbamoyl-1-methyl-ethyl)-benzyl]-nicotinamide

HRID 1297597Notes

Reaction equation

HRID 1297597 reaction equation
Cl.C[N:3](C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[O:33]1[C:37]2[CH:38]=[CH:39][C:40]([O:42][C:43]3[C:48]([C:49]([NH:51][CH2:52][C:53]4[CH:58]=[CH:57][C:56]([C:59]([CH3:64])([CH3:63])[C:60]([OH:62])=O)=[CH:55][CH:54]=4)=[O:50])=[CH:47][CH:46]=[CH:45][N:44]=3)=[CH:41][C:36]=2[O:35][CH2:34]1>O1CCCC1>[O:33]1[C:37]2[CH:38]=[CH:39][C:40]([O:42][C:43]3[N:44]=[CH:45][CH:46]=[CH:47][C:48]=3[C:49]([NH:51][CH2:52][C:53]3[CH:58]=[CH:57][C:56]([C:59]([C:60](=[O:62])[NH2:3])([CH3:63])[CH3:64])=[CH:55][CH:54]=3)=[O:50])=[CH:41][C:36]=2[O:35][CH2:34]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 98242372-[4-({[2-(Benzo[1,3]dioxol-5-yloxy)-pyridine-3-carbonyl]-amino}-methyl)-phenyl]-2-methyl-propionic acid

Product 1

HCID 102965312-(Benzo[1,3]dioxol-5-yloxy)-N-[4-(1-carbamoyl-1-methyl-ethyl)-benzyl]-nicotinamideYield 44.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.71 g), 1-hydoxybenzo-triazole hydrate (1.24 g), and were combined and suspended in anhydrous tetrahydrofuran (45 mL). N,N-Diisopropylethylamine (5.93 mL) was added to the suspension, which was stirred for 0.5 h. 2-[4-({[2-(Benzo[1,3]dioxol-5-yloxy)-pyridine-3-carbonyl]-amino}-methyl)-phenyl]-2-methyl-propionic acid (0.340 g) was added to the suspension, and the reaction mixture stirred at ambient temperature overnight. Anhydrous ammonia gas was bubbled into the solution for 20 min, generating a white precipitate, and then the reaction mixture was concentrated in vacuo. Water was added to the reaction mixture, and it was extracted with dichloromethane (7×30 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography (ethyl acetate) and further purified by silica gel chromatography (ethyl acetate:hexanes 17:3) to yield the title compound (0.150 g).

Workup

  1. stirringthe reaction mixture stirred at ambient temperature overnight
  2. customAnhydrous ammonia gas was bubbled into the solution for 20 min
  3. concentrationthe reaction mixture was concentrated in vacuo
  4. additionWater was added to the reaction mixture, and it
  5. extractionwas extracted with dichloromethane (7×30 mL)
  6. dry with materialThe combined organics were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by silica gel chromatography (ethyl acetate)
  10. customfurther purified by silica gel chromatography (ethyl acetate:hexanes 17:3)

Sources & evidence

ORD record
ord-8f26a4e0c36f4dda86a206c413206dc1
Source dataset
uspto-grants-2007_07
Patent number
US07250518B2

Reaction notes

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