Dimethylformamide → Sutetinib

HRID 403661Notes

Reaction equation

HRID 403661 reaction equation
Cl.[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7](O)=[O:8].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][C:32]=1[O:33][CH2:34][CH3:35])[N:29]=[CH:28][C:27]([C:36]#[N:37])=[C:26]2[NH:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([C:45]#[CH:46])[CH:40]=1>C1COCC1.CN1CCCC1=O>[C:36]([C:27]1[CH:28]=[N:29][C:30]2[C:25]([C:26]=1[NH:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([C:45]#[CH:46])[CH:40]=1)=[CH:24][C:23]([NH:22][C:7](=[O:8])/[CH:6]=[CH:5]/[CH2:4][N:3]([CH3:10])[CH3:2])=[C:32]([O:33][CH2:34][CH3:35])[CH:31]=2)#[N:37]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 593827436-Amino-7-ethoxy-4-(3-ethynylphenylamino)quinoline-3-carbonitrile

Product 1

HCID 49870541SutetinibYield 88.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of (E)-4-(dimethylamino)but-2-enoic acid hydrochloride (1.28 g, 7.73 mmol, 2.1 equiv) in THF (18 ml) and a catalytic amount of DMF was cooled to 5° C. while oxalyl chloride (0.67 ml, 0.007 mol, 1.9 equiv) was added slowly. The reaction mixture was then warmed to room temperature and stirred for 3 hours. A solution of 6-amino-7-ethoxy-4-(3-ethynylphenylamino)quinoline-3-carbonitrile (1.2 g, 3.66 mmol, 1.00 equiv) in N-methyl-2-pyrrolidinone (15 ml) was added dropwise over 10 minutes. The mixture was stirred for overnight, quenched with water (200 ml). Aqueous sodium hydroxide was added to bring the pH to 11. The mixture was stirred for 1 hour which formed precipitate. The resulting precipitate was filtered and washed with water and the wet solid was dried to give 1.43 g product. MS (ESI) m/z: 563 (M+1).

Workup

  1. additionwas added slowly
  2. stirringThe mixture was stirred for overnight
  3. customquenched with water (200 ml)
  4. additionAqueous sodium hydroxide was added
  5. stirringThe mixture was stirred for 1 hour which
  6. customformed precipitate
  7. filtrationThe resulting precipitate was filtered
  8. washwashed with water
  9. customthe wet solid was dried

Sources & evidence

ORD record
ord-26ca7353578a41568376159fcd3e7e1f
Source dataset
uspto-grants-2014_06
Patent number
US08748453B2

Reaction notes

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