Diisopropylethylamine → Perhydro-1, 4-oxazepine-4-carboxylic acid ((S)-1-{(S)-1-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-butyl)-amide

HRID 1455605Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1455605
[F:1][C:2]([F:19])([CH3:18])[CH2:3][C@H:4]([NH:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)=[O:10])[C:5]([OH:7])=O.Cl.[NH2:21][CH:22]([CH2:33][CH3:34])[C@@H:23]([C:25]1[O:29][N:28]=[C:27]([CH:30]2[CH2:32][CH2:31]2)[N:26]=1)[OH:24].C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>ClCCl>[CH:30]1([C:27]2[N:26]=[C:25]([CH:23]([OH:24])[C@@H:22]([NH:21][C:5]([C@@H:4]([NH:8][C:9]([N:11]3[CH2:17][CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[O:10])[CH2:3][C:2]([F:1])([F:19])[CH3:18])=[O:7])[CH2:33][CH3:34])[O:29][N:28]=2)[CH2:31][CH2:32]1

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57535332(S)-4,4-Difluoro-2-[(perhydro-1,4-oxazepine-4-carbonyl)-amino]-pentanoic acidHCID 68820971(S)-2-amino-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-butan-1-ol hydrochloride

Produkt 1

HCID 86607352Perhydro-1, 4-oxazepine-4-carboxylic acid ((S)-1-{(S)-1-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-butyl)-amideAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a mixture of (S)-4,4-Difluoro-2-[(perhydro-1,4-oxazepine-4-carbonyl)-amino]-pentanoic acid (97 mg, 0.35 mmol), (S)-2-Amino-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-butan-1-ol hydrochloride (83 mg, 0.36 mmol) and diisopropylethyl amine (121 μL, 0.70 mmol) in dry dichloromethane (12 mL) is added 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (66 mg, 0.35 mmol) and 1-hydroxybenzotriazole hydrate (47 mg, 0.35 mmol). The mixture is stirred at room temperature for 16 hr then is diluted with dichloromethane (20 mL) and washed with dilute HCl (30 mL), then saturated NaHCO3 (30 mL). The organic layer is dried (Na2SO4) and concentrated in vacuum. The residue is purified over 12 g silica gel, eluting with ethyl acetate: heptane (gradient 50-100%) to afford Perhydro-1,4-oxazepine-4-carboxylic acid ((S)-1-{(S)-1-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-butyl)-amide (120 mg, 75%) as a glassy solid. LC/MS 100% 460 (M+H).

Aufarbeitung

  1. washwashed with dilute HCl (30 mL)
  2. dry with materialThe organic layer is dried (Na2SO4)
  3. concentrationconcentrated in vacuum
  4. customThe residue is purified over 12 g silica gel
  5. washeluting with ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-c0c33300fd8f4740a0e62b5e40a25f39
Quelldatensatz
uspto-grants-2009_01
Patentnummer
US07482448B2

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