Hydrochloric Acid → 3,4-Dihydro-1H-isoquinoline-2-carboxylic Acid [4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amide

HRID 1183891

Reaktionsgleichung

Reaktionsgleichung von HRID 1183891
O=C1CCC(=O)N1O[C:9]([NH:11][C:12]1[CH:28]=[CH:27][C:15]([O:16][CH2:17][CH2:18][NH:19]C(=O)OC(C)(C)C)=[C:14]([C:29]2[N:33]([CH3:34])[N:32]=[CH:31][CH:30]=2)[CH:13]=1)=[O:10].CN(C)C=O.[CH2:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH2:43][CH2:42][NH:41]1.Cl.CCOCC>Cl>[NH2:19][CH2:18][CH2:17][O:16][C:15]1[CH:27]=[CH:28][C:12]([NH:11][C:9]([N:41]2[CH2:42][CH2:43][C:44]3[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=3)[CH2:40]2)=[O:10])=[CH:13][C:14]=1[C:29]1[N:33]([CH3:34])[N:32]=[CH:31][CH:30]=1

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6228DimethylformamideHCID 70461,2,3,4-TetrahydroisoquinolineHCID 86633178tert-butyl {2-[4-({[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}amino)-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]ethyl}carbamate

Produkt 1

HCID 578145663,4-Dihydro-1H-isoquinoline-2-carboxylic Acid [4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amideAusbeute 42,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 313Hydrochloric AcidKatalysator

Versuchsvorschrift

A 2 mL aliquot of tert-butyl {2-[4-({[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}amino)-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]ethyl}carbamate in dimethylformamide (60.0 μmol) was added to 1,2,3,4-tetrahydroisoquinoline (9.59 mg, 1.2 eq) and stirred at room temperature for 18 hr. To this was added 2.0M hydrochloric acid in ether (150 μL, 5 eq) and the reaction was stirred at room temperature for 60 hr. Some of the deprotections were incomplete so 2-3 drops of concentrated hydrochloric acid was added to these and they were stirred for another 24 hr. The ether and hydrochloric acid were evaporated under a stream of nitrogen and it was purified by HPLC. The proper fractions were collected and lyophilized to afford the title compound as a white solid in 42.9% yield. LCMS m/z (%)=392 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.85 (t, J=5.81 Hz, 2 H), 3.09-3.17 (m, 2 H), 3.69 (t, J=5.6 Hz, 2 H), 3.69 (s, 3 H), 4.12 (t, J=5.56 Hz, 2 H), 4.63 (s, 2 H), 6.32 (d, J=2.02 Hz, 1 H), 7.13 (d, J=9.09 Hz, 1 H), 7.19 (s, 3 H), 7.43 (d, J=2.53 Hz, 1 H), 7.47 (d, J=1.52 Hz, 1 H), 7.57 (dd, J=9.09, 3.03 Hz, 1 H), 7.87 (s, 2 H), 8.60 (s, 1 H).

Aufarbeitung

  1. stirringthe reaction was stirred at room temperature for 60 hr
  2. additionwas added to these and they
  3. stirringwere stirred for another 24 hr
  4. customThe ether and hydrochloric acid were evaporated under a stream of nitrogen and it
  5. customwas purified by HPLC
  6. customThe proper fractions were collected

Quellen und Nachweise

ORD-Eintrag
ord-07f44485fd2840b5876de34c7c53824c
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08664258B2

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