StartseiteMCPWorkbenchSkills
StartseiteWorkbenchBenachrichtigungenMein Bereich
llms.txt · MCP-AnleitungDatenschutz · Nutzungsbedingungen · Supportv1.8.0
  1. Startseite
  2. /Reaktion

Diisopropylethylamine → 4-(3-Amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-N-((S)-1-(3-bromo-5-fluorophenyl)-2-((N-methyl-2-nitrophenyl)sulfonamido)ethyl)-2-fluorobenzamide

HRID 596034
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 596034
[NH2:1][C:2]1[C:3]([C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[C:18]([F:25])[CH:17]=2)=[N:4][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([OH:14])[C@@H:10]([F:15])[CH2:9]2)=[CH:6][N:7]=1.Cl.[NH2:27][C@@H:28]([C:44]1[CH:49]=[C:48]([F:50])[CH:47]=[C:46]([Br:51])[CH:45]=1)[CH2:29][N:30]([CH3:43])[S:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[N+:40]([O-:42])=[O:41])(=[O:33])=[O:32].CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.O>[NH2:1][C:2]1[C:3]([C:16]2[CH:24]=[CH:23][C:19]([C:20]([NH:27][C@@H:28]([C:44]3[CH:49]=[C:48]([F:50])[CH:47]=[C:46]([Br:51])[CH:45]=3)[CH2:29][N:30]([CH3:43])[S:31]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[N+:40]([O-:42])=[O:41])(=[O:33])=[O:32])=[O:21])=[C:18]([F:25])[CH:17]=2)=[N:4][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([OH:14])[C@@H:10]([F:15])[CH2:9]2)=[CH:6][N:7]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1180458824-(3-amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-2-fluorobenzoic acidHCID 118046149(S)-N-(2-amino-2-(3-bromo-5-fluorophenyl)ethyl)-N-methyl-2-nitrobenzenesulfonamide hydrochloride

Produkt

1
HCID 1180455334-(3-Amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-N-((S)-1-(3-bromo-5-fluorophenyl)-2-((N-methyl-2-nitrophenyl)sulfonamido)ethyl)-2-fluorobenzamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To a solution of 4-(3-amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-2-fluorobenzoic acid (300 g, 95% assay, 815.8 mmol) and (S)—N-(2-amino-2-(3-bromo-5-fluorophenyl)ethyl)-N-methyl-2-nitrobenzenesulfonamide hydrochloride (397.7 g, 848.5 mmol) in DMF (2.5 kg) was added DIPEA (421.8 g, 3263.4 mmol), followed by EDCl (312.8 g, 1631.7 mmol) and HOAt (222.1 g, 1631.7 mmol). After the reaction mixture was stirred at 25° C. for 18 hours, the reaction temperature was lowered to 10° C. before IPAC (3.5 kg) and water (4.0 kg) was added. The mixture was stirred for 10 minutes and then the layers were separated. The aqueous layer was extracted with IPAC (2.5 kg). The combined organic layers were washed successively with 10% aqueous Na2CO3 (4.5 kg) and water (2×4 kg), and then concentrated under vacuum (<100 mbar) at 40-45° C. to give 4-(3-amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-N—((S)-1-(3-bromo-5-fluorophenyl)-2-(N-methyl-2-nitrophenylsulfonamido)ethyl)-2-fluorobenzamide as a foam (670 g, assay purity is 93%), which was used in next step without further purification. ESI-MS (m/z): 763.1216, 765.1161 ([M+H]+, 100). Mp=115-117° C. HPLC (method A), retention time=10.57 min. 1H NMR (400 MHz, CDCl3): 8.11 (t, J=8 Hz, 1H), 7.99 (m, 1H), 7.91 (s, 1H), 7.59-7.72 (m, 5H), 7.35 (s, 1H), 7.19 (d, J=8 Hz, 1H), 7.09 (d, J=8 Hz, 1H), 5.46 (br. s, 1H), 4.77 (br. s, 2H), 4.48-4.55, 4.35-4.42 (m, 1H), 3.93 (q, J1=12 Hz, J1=16 Hz, 1H), 3.73-3.82 (m, 1H), 3.33 (q, J1=4 Hz, J1=12 Hz, 1H), 3.00 (s, 3H), 2.78-2.85 (m, 1H), 2.31-2.37 (m, 1H), 2.12-2.20 (m, 1H), 1.84-1.96 (m, 2H), 1.60-1.71 (m, 1H), 1.47-1.56 (m, 1H).

Aufarbeitung

  1. additionwas added
  2. stirringThe mixture was stirred for 10 minutes
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with IPAC (2.5 kg)
  5. washThe combined organic layers were washed successively with 10% aqueous Na2CO3 (4.5 kg) and water (2×4 kg)
  6. concentrationconcentrated under vacuum (<100 mbar) at 40-45° C.

Quellen und Nachweise

ORD-Eintrag
ord-59283c6d4530474abd484553f2ff5616
Quelldatensatz
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09242996B2

Notizen zur Reaktion

Wird geladen…

Auf dieser SeiteKomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion