Diisopropylethylamine → (r/s)-2-Hydroxy-2-methyl-n-[(s)-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7-dihydro-5h-dibenzo[b,d]azepin-7-yl]-n-(2,2,3,3,3-pentafluoro-propyl)-malonamide

HRID 1984562Notes

Reaction equation

HRID 1984562 reaction equation
N[C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([F:14])([F:13])[F:12])[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[C:4]2[CH:19]=[CH:20][CH:21]=[CH:22][C:3]1=2.[OH:23][C:24]([CH3:39])([C:28]([NH:30][CH2:31][C:32]([F:38])([F:37])[C:33]([F:36])([F:35])[F:34])=[O:29])[C:25]([OH:27])=O.O.O[N:42]1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>O1CCCC1>[OH:23][C:24]([CH3:39])([C:25]([NH2:42])=[O:27])[C:28]([N:30]([C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([F:14])([F:12])[F:13])[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[C:4]2[CH:19]=[CH:20][CH:21]=[CH:22][C:3]1=2)[CH2:31][C:32]([F:38])([F:37])[C:33]([F:36])([F:35])[F:34])=[O:29]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 21091408HCID 21091408, compoundHCID 68848895HCID 68848895, compound

Product 1

HCID 87615152(r/s)-2-Hydroxy-2-methyl-n-[(s)-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7-dihydro-5h-dibenzo[b,d]azepin-7-yl]-n-(2,2,3,3,3-pentafluoro-propyl)-malonamideYield 79.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 144 mg (0.47 mmol) (S)-7-amino-5-(2,2,2-trifluoro-ethyl)-5H,7H-dibenzo[b,d]azepin-6-one and 125 mg (0.47 mmol) (RS)-2-hydroxy-2-methyl-N-(2,2,3,3,3-pentafluoro-propyl)-malonamic acid in 21 ml tetrahydrofuran were reacted at room temperature with 73.6 mg (0.47 mmol) 1-hydroxy-benzotriazole hydrate, 165 μl (0.94 mmol) diisopropylethylamine and 92.1 mg (0.47 mmol) N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride. Stirring was continued overnight. Removal of the solvent by distillation and chromatography on silicagel with ethylacetate/heptane (gradient 15/85 to 40/60) yielded 207 mg (79%) (R/S)-2-hydroxy-2-methyl-N-[(S)-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-N-(2,2,3,3,3-pentafluoro-propyl)-malonamide as a white solid, MS (m/e): 554.3 (M+H)+.

Workup

  1. customRemoval of the solvent
  2. distillationby distillation and chromatography on silicagel with ethylacetate/heptane (gradient 15/85 to 40/60)

Sources & evidence

ORD record
ord-2c0966da967844ed84416e8e50200527
Source dataset
uspto-grants-2009_06
Patent number
US07544679B2

Reaction notes

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