Diisopropylethylamine → HCID 57713974, compound

HRID 1984561Notes

Reaction equation

HRID 1984561 reaction equation
[NH2:1][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]([CH3:37])([C:28]([NH:30][CH2:31][CH2:32][C:33]([F:36])([F:35])[F:34])=[O:29])[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>[OH:23][C:24]([CH3:37])([C:28]([NH:30][CH2:31][CH2:32][C:33]([F:34])([F:35])[F:36])=[O:29])[C:25]([NH:1][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)=[O:26]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 210914092-Hydroxy-2-methyl-N-(3,3,3-trifluoro-propyl)-malonamic acidHCID 68848895HCID 68848895, compound

Product 1

HCID 57713974HCID 57713974, compoundYield 65.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 200 mg (0.65 mmol) (S)-7-amino-5-(2,2,2-trifluoro-ethyl)-5H,7H-dibenzo[b,d]azepin-6-one and 150 mg (0.65 mmol) (RS)-2-hydroxy-2-methyl-N-(3,3,3-trifluoro-propyl)-malonamic acid in 7 ml tetrahydrofuran were cooled to 0° C. and 102 mg (0.65 mmol) 1-hydroxy-benzotriazole hydrate, 228 μl (1.31 mmol) diisopropylethylamine and 128 mg (0.65 mmol) N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride were added. Stirring was continued overnight at room temperature. Removal of the solvent by distillation and chromatography on silicagel with ethylacetate/heptane (gradient 1/4 to 4/1) yielded 220 mg (65%) (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′-(3,3,3-trifluoro-propyl)-malonamide as a white solid, MS (m/e): 518.2 (M+H)+.

Workup

  1. customRemoval of the solvent
  2. distillationby distillation and chromatography on silicagel with ethylacetate/heptane (gradient 1/4 to 4/1)

Sources & evidence

ORD record
ord-781b3c319b7d4b128622aa436a75b9f9
Source dataset
uspto-grants-2009_06
Patent number
US07544679B2

Reaction notes

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