Diisopropylethylamine → 4-[(2-Methoxy-ethyl)-methyl-amino]-but-2-enoic Acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide Dihydrochloride

HRID 548466Notes

Reaction equation

HRID 548466 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[CH:7][C:6]([C:14]#[N:15])=[C:5]2[NH:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[C:19]([Cl:24])[CH:18]=1.C(N(C(C)C)CC)(C)C.Br[CH2:35]/[CH:36]=[CH:37]/[C:38]([Cl:40])=[O:39].[CH3:41][O:42][CH2:43][CH2:44][NH:45][CH3:46].C(=O)(O)[O-].[Na+]>O1CCCC1>[ClH:24].[ClH:40].[Cl:24][C:19]1[CH:18]=[C:17]([NH:16][C:5]2[C:4]3[C:9](=[CH:10][C:11]([O:12][CH3:13])=[C:2]([NH:1][C:38](=[O:39])[CH:37]=[CH:36][CH2:35][N:45]([CH2:44][CH2:43][O:42][CH3:41])[CH3:46])[CH:3]=3)[N:8]=[CH:7][C:6]=2[C:14]#[N:15])[CH:22]=[CH:21][C:20]=1[F:23]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 300977(2-Methoxyethyl)(methyl)amineHCID 516892Sodium BicarbonateHCID 111424366-Amino-4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinoline-3-carbonitrileHCID 11263885(E)-4-Bromo-2-butenoyl Chloride

Product 1

HCID 672028284-[(2-Methoxy-ethyl)-methyl-amino]-but-2-enoic Acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide Dihydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring solution of 1.2 g (3.5 mmol) of 6-amino-4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinoline-3-carbonitrile and 0.52 g (4.0 mmol) of diisopropylethylamine in 40 ml of tetrahydrofuran at 0° C. was added a solution of 4-bromo crotonyl chloride in 10 ml of tetrahydrofuran. After 45 min, 1.87 (21 mmol) of 2-methoxyethyl methyl amine was added. After 1 hr at room temperature, the mixture was poured into a solution of sodium bicarbonate and extracted with ethyl acetate. The organic solution was dried over magnesium sulfate. The solvent was removed and the residue was purified by chromatography on silica gel. Product eluted with ethyl acetate-methanol-triethylamine 40:8:1 giving 0.87 g of the free base. This was dissolved in 20 ml of ethyl acetate and 10 ml of a solution of hydrogen chloride in ether was added. The solid was collected giving 1.02 g of the title compound as a yellow powder: mass spectrum (electrospray, m/e): M+H 498.0, (M+2H)+2248.5.

Workup

  1. waitAfter 1 hr at room temperature
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic solution was dried over magnesium sulfate
  4. customThe solvent was removed
  5. customthe residue was purified by chromatography on silica gel
  6. washProduct eluted with ethyl acetate-methanol-triethylamine 40:8:1 giving 0.87 g of the free base
  7. dissolutionThis was dissolved in 20 ml of ethyl acetate
  8. addition10 ml of a solution of hydrogen chloride in ether was added
  9. customThe solid was collected

Sources & evidence

ORD record
ord-f2a28531170f4a7e87531fc6501c665c
Source dataset
uspto-grants-2011_05
Patent number
USRE042376E1

Reaction notes

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