Dimethylformamide → HCID 71744790, compound

HRID 530212Notes

Reaction equation

HRID 530212 reaction equation
[CH3:1][N:2]([CH:4]=O)[CH3:3].C(Cl)(=O)C(Cl)=O.[NH2:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[O:23][CH2:24][CH3:25])[N:19]=[CH:18][C:17]([C:26]#[N:27])=[C:16]2[NH:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[CH:31][CH:30]=1.[CH2:42]1C[O:45][CH2:44][CH2:43]1>CN1CCCC1=O>[C:26]([C:17]1[CH:18]=[N:19][C:20]2[C:15]([C:16]=1[NH:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[CH:31][CH:30]=1)=[CH:14][C:13]([NH:12][C:44](=[O:45])/[CH:43]=[CH:42]/[CH2:4][N:2]([CH3:1])[CH3:3])=[C:22]([O:23][CH2:24][CH3:25])[CH:21]=2)#[N:27]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 65578Oxalyl chlorideHCID 89852606HCID 89852606, compound

Product 1

HCID 71744790HCID 71744790, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 4-N,N-dimethyl-aminocrotonic acid hydrochloride (1.28 g) in THF (18 mL) and a catalytic amount of DMF was cooled to 5° C., the oxalyl chloride (0.67 mL) was added dropwise. The mixture was then warmed to room temperature and stirred for 3 hours. A solution of 6-amino-7-ethoxy-4-((4-phenoxyphenyl)amino)quinoline-3-carbonitrile in N-methyl-2-pyrrolidinone (20 ml) was added dropwise over 10 minutes. The reaction mixture was stirred overnight and then quenched with water. Aqueous sodium hydroxide was added slowly to bring the pH to 11. It was stirred for another 1 hour and the resulting precipitate was filtered and washed with water. The wet solid was recrystallized in acetonitrile and THF and dried to give desired product (E)-N-(3-cyano-7-ethoxy-4-((4-phenoxyphenyl)amino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide (1.56 g). 1H-NMR (400 MHz, CDCl3, ppm): 9.17 (1H, s), 8.52 (1H, s), 8.10 (1H, s), 7.37-6.97, (13H, m), 6.20 (1H, d, J=15.6 Hz), 4.32 (2H, q, J=7.2 Hz), 3.17-3.15 (2H, m), 2.31 (6H, s), 1.57-1.69 (3H, t, J=7.2 Hz). MS m/z 508.3[M+1].

Workup

  1. stirringThe reaction mixture was stirred overnight
  2. customquenched with water
  3. additionAqueous sodium hydroxide was added slowly
  4. stirringIt was stirred for another 1 hour
  5. filtrationthe resulting precipitate was filtered
  6. washwashed with water
  7. customThe wet solid was recrystallized in acetonitrile
  8. dry with materialTHF and dried

Sources & evidence

ORD record
ord-2fcfaf0052f641cead1bbf57f8b4cfc9
Source dataset
uspto-grants-2016_05
Patent number
US09353062B2

Reaction notes

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