Triethylamine → 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide

HRID 2172330Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2172330
[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:8]=2[C:17]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:18]=2[CH2:19][CH2:20][NH:21][CH2:22]3)=[CH:5][CH:4]=[N:3]1.O=C1N([S:33]([NH:36][C:37]2[N:42]=[CH:41][CH:40]=[CH:39][N:38]=2)(=[O:35])=[O:34])CCO1.C(N(CC)CC)C>C(#N)C>[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[C:11]([C:13]([F:16])([F:14])[F:15])[CH:10]=[CH:9][C:8]=2[C:17]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:18]=2[CH2:19][CH2:20][N:21]([S:33]([NH:36][C:37]2[N:42]=[CH:41][CH:40]=[CH:39][N:38]=2)(=[O:35])=[O:34])[CH2:22]3)=[CH:5][CH:4]=[N:3]1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 898134912-oxo-N-(pyrimidin-2-yl)oxazolidine-3-sulfonamide2×HCID 898152865-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline2×

Produkt 1

HCID 717370675-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamideAusbeute 41,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A microwave vial was charged with 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (Intermediate O, 55.90 mg, 0.156 mmol), 2-oxo-N-(pyrimidin-2-yl)oxazolidine-3-sulfonamide (Intermediate Q, 96 mg, 0.391 mmol), and acetonitrile (587 μl) to give a suspension. Triethylamine (218 μl, 1.564 mmol) was added resulting in the formation of a yellow solution. The vial was sealed and heated in a microwave reactor for 30 min at 130° C. The mixture was concentrated, then chromatographed on a 12 g silica gel column with 0 to 10% MeOH/DCM to provide 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (33.42 mg, 0.065 mmol) as a light-yellow solid. [M+H]+=515.2. 1H NMR (400 MHz, DMSO-d6) δ ppm=11.19 (br. s., 1H), 8.48 (d, J=4.9 Hz, 2H), 7.88 (dd, J=1.4, 8.1 Hz, 1H), 7.83 (br. s, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.22 (d, J=2.0 Hz, 1H), 7.20-7.10 (m, 2H), 7.03 (t, J=4.8 Hz, 1H), 6.89 (dd, J=1.3, 7.4 Hz, 1H), 5.88 (d, J=1.9 Hz, 1H), 4.62-4.49 (m, 2H), 3.59-3.52 (m, 1H), 3.48 (s, 3H), 3.23 (ddd, J=4.3, 8.0, 12.4 Hz, 1H), 2.59 (ddd, J=4.9, 8.3, 16.1 Hz, 1H), 2.28-2.19 (m, 1H).

Aufarbeitung

  1. customto give a suspension
  2. customresulting in the formation of a yellow solution
  3. customThe vial was sealed
  4. concentrationThe mixture was concentrated
  5. customchromatographed on a 12 g silica gel column with 0 to 10% MeOH/DCM

Quellen und Nachweise

ORD-Eintrag
ord-af51eaf5926e486c96779a471fb96f8d
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09051311B2

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