Hydrochloric Acid → 1-(2-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide

HRID 528943Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 528943
[N:1]([CH2:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][N:6]1[C:15]([C:17]1[CH:22]=[C:21]([C:23](=[O:47])[NH:24][S:25]([C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[C:31]([O:38][CH2:39][CH2:40][N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[CH:32]=[CH:33][CH:34]=3)[CH:29]=2)(=[O:27])=[O:26])[CH:20]=[CH:19][C:18]=1[N:48]1[C:52]([CH3:53])=[C:51]([Cl:54])[C:50]([C:55]([N:57]([CH2:62][CH2:63][CH2:64][CH3:65])[CH2:58][CH2:59][CH2:60][CH3:61])=[O:56])=[N:49]1)=[O:16])=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH-].[Na+].Cl>C1COCC1.O>[NH2:1][CH2:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][N:6]1[C:15]([C:17]1[CH:22]=[C:21]([C:23](=[O:47])[NH:24][S:25]([C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[C:31]([O:38][CH2:39][CH2:40][N:41]4[CH2:42][CH2:43][O:44][CH2:45][CH2:46]4)[CH:32]=[CH:33][CH:34]=3)[CH:29]=2)(=[O:27])=[O:26])[CH:20]=[CH:19][C:18]=1[N:48]1[C:52]([CH3:53])=[C:51]([Cl:54])[C:50]([C:55]([N:57]([CH2:62][CH2:63][CH2:64][CH3:65])[CH2:58][CH2:59][CH2:60][CH3:61])=[O:56])=[N:49]1)=[O:16]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 86718907(S)-1-(2-(3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide

Produkt 1

HCID 867189081-(2-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamideAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of (S)-1-(2-(3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (45 mg, 0.049 mmol) and PPh3 (38 mg, 0.15 mmol) in THF (4.0 mL) and water (0.4 mL) was added 1N aq. NaOH solution (0.2 mL, 0.20 mmol). The resulting reaction mixture was heated at 50° C. for 3 h and then acidified (pH=1) with 1N aq. HCl solution. The solvent was removed in vacuo, and the residue was purified by preparative HPLC to give the title compound (33 mg, 72%) as a white solid. 1H NMR (CD3OD, mixture of amide rotamers) δ 9.16 (s, 1H), 8.29-7.88 (m, 4H), 7.83-7.58 (m, 3H), 7.40-7.08 (m, 4H), 6.99 (br s, 1H), 5.04 (br s, 0.5H), 4.76-4.41 (m, 4H), 4.27-2.66 (m, 18.5H), 2.42-2.20 (m, 3H), 1.64-0.72 (m, 13H), 0.60 (br s, 1H); MS(ESI+) m/z 898.1 (M+H)+.

Aufarbeitung

  1. customThe resulting reaction mixture
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-3069e063c18d4a4a9576286fa8da8894
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346795B2

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