Ammonia → 2-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}isobutyramide

HRID 1530379Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1530379
[F:1][C:2]1[C:24]([S:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([CH3:37])([CH3:36])[C:33]([OH:35])=O)[CH2:28][CH2:27]2)=[CH:23][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:20]([CH3:22])[CH3:21])[N:16]=[C:17]([CH3:19])[N:18]=1)[N:7]=3.CC[N:40](C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.N.CCN=C=NCCCN(C)C>CN(C=O)C>[F:1][C:2]1[C:24]([S:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([CH3:36])([CH3:37])[C:33]([NH2:40])=[O:35])[CH2:28][CH2:27]2)=[CH:23][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:20]([CH3:21])[CH3:22])[N:16]=[C:17]([CH3:19])[N:18]=1)[N:7]=3

Komponenten

7

Edukt 5

HCID 222AmmoniaHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 683126382-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid

Produkt 1

HCID 683130762-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}isobutyramideAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a suspension of 2-{4-[8-fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid (174 mg, 0.329 mmol) in DMF (5 mL) were added DIPEA (169 l, 0.987 mmol), HOBt.NH3 (75 mg, 0.494 mmol) and EDCI (95 mg, 0.494 mmol) and the reaction mixture was stirred at RT for 18 h. The mixture was then partitioned between EtOAc and water and the aqueous phase was further extracted with EtOAc (×3). The combined organic layers were washed with water, followed by brine, then dried and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 3-15% MeOH in DCM) affording the title compound as a colorless sticky solid (96 mg, 56%). LCMS: RT 2.16 min [M+H]+ 527.8

Aufarbeitung

  1. customThe mixture was then partitioned between EtOAc and water
  2. extractionthe aqueous phase was further extracted with EtOAc (×3)
  3. washThe combined organic layers were washed with water
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 3-15% MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-0a27cf6948d046f8992011e0d0da0f77
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090628B2

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