Oxalyl chloride → (2E)-4-(Dimethylamino)-2-butenoyl chloride

HRID 929841Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 929841
Cl.[CH3:2][N:3](/[C:5](=[CH:9]\[CH3:10])/[C:6](O)=O)[CH3:4].[C:11](Cl)(=[O:15])[C:12]([Cl:14])=[O:13].[NH2:17][C:18]1[N:23]=[C:22]([NH:24][C:25]2[CH:30]=[C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[CH:34][CH:33]=3)[N:28]=[CH:27][N:26]=2)[CH:21]=[CH:20][CH:19]=1>CC#N.CN(C=O)C.CN1C(=O)CCC1.CCOC(C)=O>[CH3:4][N:3]([CH2:5]/[CH:9]=[CH:10]/[C:12]([Cl:14])=[O:13])[CH3:2].[CH3:2][N:3]([CH3:4])[CH2:5]/[CH:6]=[CH:12]/[C:11]([NH:17][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([NH:24][C:25]2[CH:30]=[C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)=[CH:34][CH:33]=3)[N:28]=[CH:27][N:26]=2)[N:23]=1)=[O:15]

Komponenten

9

Edukt 3

HCID 65578Oxalyl chlorideHCID 57708269N4-(6-aminopyridin-2-yl)-N6-4-phenoxyphenylpyrimidine-4,6-diamineHCID 86630629Dimethylaminocrotonic acid hydrochloride

Produkt 2

HCID 10012053(2E)-4-(Dimethylamino)-2-butenoyl chlorideHCID 42602745(E)-4-(dimethylamino)-N-(6-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)pyridine-2-yl)but-2-enamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6228DimethylformamideKatalysatorHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of dimethylaminocrotonyl chloride was prepared by reaction of dimethylaminocrotonic acid hydrochloride (0.36 g, 2.16 mmol) in CH3CN (4 mL) containing DMF (1 drop) with oxalyl chloride (0.34 g, 2.70 mmol) according to the procedure in Example 15a. This acid chloride was added drop wise at 0° C. in to a stirred solution of N4-(6-aminopyridin-2-yl)-N6-4-phenoxyphenylpyrimidine-4,6-diamine (IR-11) (0.2 g, 0.54 mmol) in NMP (8 mL). The reaction was stirred at 0° C. for 1 h, was diluted with EtOAc (5 mL), and was washed with 10% NaHCO3 (2 mL), water (2 mL) and brine (2 mL). Drying over Na2SO4 followed by concentration under reduced pressure offered a residue which was further purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1) to give (E)-4-(dimethylamino)-N-(6-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)pyridine-2-yl)but-2-enamide (I-64) as a yellow solid. 1H NMR (DMSO-d6) δ ppm: 2.18 (s, 6H), 3.05 (d, J=5.2 Hz, 2H), 6.48 (d, J=15.2 Hz, H), 6.79 (d, J=6 & 15.6 Hz, 1H), 6.96-6.99 (m, 4H), 7.07-7.15 (m, 2H), 7.36 (t, J=7.6 Hz, 2H), 7.42 (s, 1H), 7.64-7.7 (m, 4H), 8.30 (s, 1H), 9.12 (s, 1H), 9.69 (s, 1H), 10.07 (s, 1H); LCMS: m/e 482.4 (M+1).

Aufarbeitung

  1. washwas washed with 10% NaHCO3 (2 mL), water (2 mL) and brine (2 mL)
  2. dry with materialDrying over Na2SO4
  3. concentrationfollowed by concentration under reduced pressure
  4. customwas further purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1)

Quellen und Nachweise

ORD-Eintrag
ord-da06b56acf46433b8dfb8e184722ff34
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09296704B2

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