Diisopropylethylamine → N-((S)-5-cyclopropylmethyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)-N'-(2,2,3,3,3-pentafluoro-propyl)-malonamide

HRID 1372947Notes

Reaction equation

HRID 1372947 reaction equation
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][CH:11]2[CH2:13][CH2:12]2)[C:6]2[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=2[C:4]2[CH:18]=[CH:19][CH:20]=[CH:21][C:3]1=2.[O:22]=[C:23]([NH:28][CH2:29][C:30]([F:36])([F:35])[C:31]([F:34])([F:33])[F:32])[CH2:24][C:25](O)=[O:26].O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>O1CCCC1>[CH:11]1([CH2:10][N:7]2[C:8](=[O:9])[C@@H:2]([NH:1][C:25](=[O:26])[CH2:24][C:23]([NH:28][CH2:29][C:30]([F:36])([F:35])[C:31]([F:32])([F:34])[F:33])=[O:22])[C:3]3[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=3[C:5]3[CH:17]=[CH:16][CH:15]=[CH:14][C:6]2=3)[CH2:13][CH2:12]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 21072520HCID 21072520, compoundHCID 68916092HCID 68916092, compound

Product 1

HCID 86596822N-((S)-5-cyclopropylmethyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)-N'-(2,2,3,3,3-pentafluoro-propyl)-malonamideYield 90.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

0.11 g (0.38 mmol) (S)-7-Amino-5-cyclopropylmethyl-5H,7H-dibenzo[b,d]azepin-6-one and 0.09 g (0.38 mmol) 3-oxo-3-(2,2,3,3,3-pentafluoro-propylamino)-propanoic acid in 10 ml tetrahydrofuran were reacted with 0.06 g (0.38 mmol) 1-hydroxybenzotriazole hydrate, 0.13 ul (0.76 mmol) diisopropylethylamine and 0.7 g (0.38 mmol) N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimid-hydrochlorid at 0° C. for 4 hours. After stirring at room temperature over night the solvent was removed by distillation and the residue purified by chromatography on silicagel with heptane/ethylacetate (gradient 100–0/0-100) to yield 0.17 g (89%) N-((S)-5-cyclopropylmethyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)-N′-(2,2,3,3,3-pentafluoro-propyl)-malonamide as white solid.

Workup

  1. customwas removed by distillation
  2. customthe residue purified by chromatography on silicagel with heptane/ethylacetate (gradient 100–0/0-100)

Sources & evidence

ORD record
ord-88e1978036924a49b4af644df9dd06c9
Source dataset
uspto-grants-2007_01
Patent number
US07160875B2

Reaction notes

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