Diisopropylethylamine → 1-{[4-[2-(3-Fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-2-(hex-5-enyl-methyl-carbamoyl)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

HRID 1443504Notes

Reaction equation

HRID 1443504 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[C:25]([CH3:32])[C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=4)[N:21]=3)[CH2:16][CH:15]2[C:40]([OH:42])=O)=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2].Cl.[CH2:44]([NH:50][CH3:51])[CH2:45][CH2:46][CH2:47][CH:48]=[CH2:49].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[C:25]([CH3:32])[C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=4)[N:21]=3)[CH2:16][CH:15]2[C:40](=[O:42])[N:50]([CH2:44][CH2:45][CH2:46][CH2:47][CH:48]=[CH2:49])[CH3:51])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 686865802-(1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-[2-(3-fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-cyclopentanecarboxylic acidHCID 71413963N-Methylhex-5-en-1-amine hydrochloride

Product 1

HCID 684124351-{[4-[2-(3-Fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-2-(hex-5-enyl-methyl-carbamoyl)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl esterYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compound 156 (0.81 g, 1.40 mmol) and hex-5-enyl-methyl-amine hydrochloride (272 mg, 1.82 mmol) was dissolved in dry DMF (50 mL). DIEA (975 μL, 5.6 mmol) was added and the reaction flask was placed in an ice bath. After 10 minutes HATU (559 mg, 1.47 mmol) was added to the solution. The reaction flask was allowed to reach room temperature and the stirring was continued for 3 hrs before the solvent was removed by evaporation. The crude product was extracted with CHCl3 and washed with saturated NaHCO3 (aq). The organic phase was dried (Na2SO4), evaporated on silica and purified to by flash chromatography (heptane:ethyl acetate 1:1) to give the title compound (0.716 g, 76%), LRMS (M+H) 673.

Workup

  1. customthe reaction flask was placed in an ice bath
  2. customto reach room temperature
  3. customwas removed by evaporation
  4. extractionThe crude product was extracted with CHCl3
  5. washwashed with saturated NaHCO3 (aq)
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. customevaporated on silica
  8. custompurified to by flash chromatography (heptane:ethyl acetate 1:1)

Sources & evidence

ORD record
ord-9ee09cd385e049b09a27f5c90dfce346
Source dataset
uspto-grants-2010_02
Patent number
US07659245B2

Reaction notes

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