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

HRID 1984542Notes

Reaction equation

HRID 1984542 reaction equation
[NH2:1][C@@H:2]1[C:8](=[O:9])[NH:7][C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[C:4]2[CH:14]=[CH:15][CH:16]=[CH:17][C:3]1=2.[OH:18][C:19]([CH3:34])([C:23]([NH:25][CH2:26][C:27]([F:33])([F:32])[C:28]([F:31])([F:30])[F:29])=[O:24])[C:20](O)=[O:21].O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC.Cl>O1CCCC1>[OH:18][C:19]([CH3:34])([C:23]([NH:25][CH2:26][C:27]([F:32])([F:33])[C:28]([F:29])([F:30])[F:31])=[O:24])[C:20]([NH:1][C@@H:2]1[C:8](=[O:9])[NH:7][C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[C:4]2[CH:14]=[CH:15][CH:16]=[CH:17][C:3]1=2)=[O:21]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 21091408HCID 21091408, compoundHCID 25067537(7S)-7-Amino-5,7-dihydro-6H-dibenzo[b,d]azepin-6-one

Product 1

HCID 24989818(r/s)-2-Hydroxy-2-methyl-n-((s)-6-oxo-6,7-dihydro-5h-dibenzo[b,d]azepin-7-yl)-n'-(2,2,3,3,3-pentafluoro-propyl)-malonamideYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 101 mg (0.45 mmol) (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one and 119 mg (0.45 mmol) (RS)-2-hydroxy-2-methyl-N-(2,2,3,3,3-pentafluoro-propyl)-malonamic acid in 15 ml tetrahydrofuran were cooled to 0° C. and 61.8 mg (0.45 mmol) 1-hydroxy-benzotriazole hydrate, 157 μl (0.90 mmol) diisopropylethylamine and 87.6 mg (0.45 mmol) N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride were added. Stirring was continued overnight at room temperature. The mixture was poured on ice/water and 1 N aqueous hydrochloric acid was added until pH=1 was reached. Extraction with diethylether, washing with saturated aqueous sodium hydrogen carbonate solution and brine and chromatography on silicagel with ethylacetate/cyclohexane 1/1 yielded 86.1 mg (41%) (R/S)-2-hydroxy-2-methyl-N-((S)-6-oxo-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): 472.1 (M+H)+.

Workup

  1. additionwas added until pH=1
  2. extractionExtraction with diethylether
  3. washwashing with saturated aqueous sodium hydrogen carbonate solution and brine and chromatography on silicagel with ethylacetate/cyclohexane 1/1

Sources & evidence

ORD record
ord-84fccb00a6444ed28b0ed432744df1eb
Source dataset
uspto-grants-2009_06
Patent number
US07544679B2

Reaction notes

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