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

HRID 929841Notes

Reaction equation

HRID 929841 reaction equation
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]

Participants

9

Reactant 3

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

Product 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

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-da06b56acf46433b8dfb8e184722ff34
Source dataset
uspto-grants-2016_03
Patent number
US09296704B2

Reaction notes

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