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Diisopropylethylamine → N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-1-(dimethylamino)-N-methylcyclopropane-carboxamide

HRID 912542
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 912542
[CH3:1][N:2]1[C:10]2[CH:9]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][NH:20][CH3:21])=[C:13]([C:22]([F:25])([F:24])[F:23])[CH:12]=3)[N:7]=[C:6]([C:26]#[N:27])[C:5]=2[N:4]=[CH:3]1.[CH3:28][N:29]([CH3:36])[C:30]1([C:33](O)=[O:34])[CH2:32][CH2:31]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.CCOC(C)=O.CCOCC>[C:26]([C:6]1[C:5]2[N:4]=[CH:3][N:2]([CH3:1])[C:10]=2[CH:9]=[C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][N:20]([CH3:21])[C:33]([C:30]3([N:29]([CH3:36])[CH3:28])[CH2:32][CH2:31]3)=[O:34])=[C:13]([C:22]([F:25])([F:23])[F:24])[CH:12]=2)[N:7]=1)#[N:27]
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Komponenten

8

Edukt 4

HCID 81531DiisopropylethylamineHCID 3861991-(Dimethylamino)cyclopropane-1-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594106391-methyl-6-(4-(2-(methylamino)ethoxy)-3-(trifluoromethyl)-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile

Produkt 1

HCID 59410641
N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-1-(dimethylamino)-N-methylcyclopropane-carboxamide
Ausbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3283Diethyl EtherLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

1-Methyl-6-(4-(2-(methylamino)ethoxy)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (54 mg), 1-(dimethylamino)cyclopropane-carboxylic acid (37.2 mg), HATU (82 mg) and DIPEA (0.119 ml) were combined in NMP (2 ml) and stirred at room temperature for 16 hours. The reaction mixture was diluted with EtOAc (25 mL) and washed with 1:1 saturated sodium bicarbonate solution/water (3×15 mL). Organics were dried over sodium sulphate and solvent evaporated under reduced pressure. Purification by flash chromatography (10 g silica column, DCM to 5% MeOH in DCM gradient) followed by preparative HPLC (acidic) and SCX afforded N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-1-(dimethylamino)-N-methylcyclopropane-carboxamide (22% yield) as a white solid after trituration with ether and oven drying.

Aufarbeitung

  1. washwashed with 1:1 saturated sodium bicarbonate solution/water (3×15 mL)
  2. dry with materialOrganics were dried over sodium sulphate and solvent
  3. customevaporated under reduced pressure
  4. customPurification by flash chromatography (10 g silica column, DCM to 5% MeOH in DCM gradient)

Quellen und Nachweise

ORD-Eintrag
ord-472a3a2fd6d0491291a28075a3cb5f03
Quelldatensatz
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08026236B2

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