N,N-Dimethylglycine → N-[4-[2-(2-Dimethylamino-acetylamino)-ethoxy]-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-methoxy-benzamide

HRID 1183883Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1183883
[CH3:1][N:2]([CH3:7])[CH2:3][C:4](O)=[O:5].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:40][CH2:41][CH2:42][O:43][C:44]1[CH:49]=[CH:48][C:47]([NH:50][C:51](=[O:60])[C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([O:58][CH3:59])[CH:53]=2)=[CH:46][C:45]=1[C:61]1[N:65]([CH3:66])[N:64]=[CH:63][CH:62]=1.CCOCC>ClCCl.Cl>[CH3:1][N:2]([CH3:7])[CH2:3][C:4]([NH:40][CH2:41][CH2:42][O:43][C:44]1[CH:49]=[CH:48][C:47]([NH:50][C:51](=[O:60])[C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([O:58][CH3:59])[CH:53]=2)=[CH:46][C:45]=1[C:61]1[N:65]([CH3:66])[N:64]=[CH:63][CH:62]=1)=[O:5]

Komponenten

8

Edukt 5

HCID 673N,N-DimethylglycineHCID 3283Diethyl EtherHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67265457N-(4-(2-aminoethoxy)-3-(1-methyl-1H-pyrazol-5-yl)phenyl)-3-methoxybenzamide hydrochloride

Produkt 1

HCID 57814700N-[4-[2-(2-Dimethylamino-acetylamino)-ethoxy]-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-methoxy-benzamideAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

2-(dimethylamino)acetic acid (16.0 mg, 1.25 eq), triethylamine (34.6 mL, 2.0 eq) and HATU (59.0 mg, 1.25 eq) were dissolved in 3 mL of dichloromethane and stirred at room temperature for 10 minutes. At this time N-(4-(2-aminoethoxy)-3-(1-methyl-1H-pyrazol-5-yl)phenyl)-3-methoxybenzamide hydrochloride (50.0 mg, 124 μmol) dissolved in 2.0 mL of dichloromethane was added and the reaction was stirred at room temperature for 3 hr. The solvents were evaporated under a stream of nitrogen and it was purified by HPLC. The proper fractions were collected and lyophilized. It was then stirred overnight in 2.0M hydrochloric acid in ether (310.3 μl, 5 eq). The solvents were evaporated under a stream of nitrogen and lyophilized to afford the title compound as a white solid in 43.0% yield. LCMS m/z (%)=452 (M+H, 100). 1H NMR (400 MHz, CDCl3) δ ppm 2.83 (s, 3 H), 2.90 (s, 3 H), 3.61-3.67 (m, 2 H), 3.82 (s, 2 H), 3.87 (s, 3 H), 3.88 (s, 3 H), 4.07 (t, J=4.55 Hz, 2 H), 6.42 (d, J=2.53 Hz, 1 H), 6.99 (d, J=8.59 Hz, 1 H), 7.10 (dt, J=4.55, 2.53 Hz, 1 H), 7.40 (d, J=5.05 Hz, 2 H), 7.44 (s, 1 H), 7.57 (dd, J=9.09, 2.53 Hz, 1 H), 7.70 (d, J=2.53 Hz, 1 H), 7.82 (d, J=2.53 Hz, 1 H)

Aufarbeitung

  1. additionwas added
  2. stirringthe reaction was stirred at room temperature for 3 hr
  3. customThe solvents were evaporated under a stream of nitrogen and it
  4. customwas purified by HPLC
  5. customThe proper fractions were collected
  6. customThe solvents were evaporated under a stream of nitrogen

Quellen und Nachweise

ORD-Eintrag
ord-51107734a5384e08ad49c7c6d594d51c
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08664258B2

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