Dichloromethane → 8-[2,6-dichloro-3-[N-methyl-N-[(E)-3-[6-(4-pyridylacetamido)pyridin-3-yl]acryloylglycyl]amino]-benzyloxy]-2-methyl-4-(2-pyridylmethoxy)quinoline

HRID 365570Notes

Reaction equation

HRID 365570 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]([NH:12][CH2:13][C:14]([N:16]([C:18]2[C:19]([Cl:46])=[C:20]([C:42]([Cl:45])=[CH:43][CH:44]=2)[CH2:21][O:22][C:23]2[CH:24]=[CH:25][CH:26]=[C:27]3[C:32]=2[N:31]=[C:30]([CH3:33])[CH:29]=[C:28]3[O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=2)[CH3:17])=[O:15])=[O:11])=[CH:4][CH:3]=1.C(N(CC)CC)C.ClCCl.Cl.[N:58]1[CH:63]=[CH:62][C:61]([CH2:64][C:65](Cl)=[O:66])=[CH:60][CH:59]=1>O>[Cl:46][C:19]1[C:18]([N:16]([CH3:17])[C:14](=[O:15])[CH2:13][NH:12][C:10](=[O:11])/[CH:9]=[CH:8]/[C:5]2[CH:6]=[N:7][C:2]([NH:1][C:65](=[O:66])[CH2:64][C:61]3[CH:62]=[CH:63][N:58]=[CH:59][CH:60]=3)=[CH:3][CH:4]=2)=[CH:44][CH:43]=[C:42]([Cl:45])[C:20]=1[CH2:21][O:22][C:23]1[CH:24]=[CH:25][CH:26]=[C:27]2[C:32]=1[N:31]=[C:30]([CH3:33])[CH:29]=[C:28]2[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 232920204-Pyridineacetyl chloride hydrochlorideHCID 232920288-[3-[N-[(E)-3-(6-aminopyridin-3-yl)acryloylglycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2-methyl-4-(2-pyridylmethoxy)quinoline

Product 1

HCID 113202628-[2,6-dichloro-3-[N-methyl-N-[(E)-3-[6-(4-pyridylacetamido)pyridin-3-yl]acryloylglycyl]amino]-benzyloxy]-2-methyl-4-(2-pyridylmethoxy)quinolineYield 9.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 8-[3-[N-[(E)-3-(6-aminopyridin-3-yl)acryloylglycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2-methyl-4-(2-pyridylmethoxy)quinoline (90 mg), triethylamine (56 mg) and dichloromethane (2 ml) was added 4-pyridylacetyl chloride hydrochloride (53 mg) in ice water bath under nitrogen atmosphere, and the mixture was stirred for 1 hour at the same temperature and allowed to stand for 1 day at ambient temperature. The reaction mixture was poured into water and extracted with chloroform. The organic layer was washed with water and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by preparative thin layer chromatography (chloroform:methanol=10:1, V/V) to give 8-[2,6-dichloro-3-[N-methyl-N-[(E)-3-[6-(4-pyridylacetamido)pyridin-3-yl]acryloylglycyl]amino]-benzyloxy]-2-methyl-4-(2-pyridylmethoxy)quinoline (10 mg) as an amorphous powder.

Workup

  1. waitto stand for 1 day at ambient temperature
  2. extractionextracted with chloroform
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated in vacuo
  6. customThe residue was purified by preparative thin layer chromatography (chloroform:methanol=10:1, V/V)

Sources & evidence

ORD record
ord-548575f98ce747e1a3726e854d0aebab
Source dataset
uspto-grants-2000_10
Patent number
US06127389

Reaction notes

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