1,2-Dichloroethane → N1-(4-(2-(3-(tert-Butyldimethylsilyloxy)azetidine-1-carbonyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide

HRID 418690Notes

Reaction equation

HRID 418690 reaction equation
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]([N:18]4[CH2:21][CH:20]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH2:19]4)=[O:17])[S:15][C:8]=23)=[C:4]([F:32])[CH:3]=1.[CH3:33][O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[NH:41][C:42](=[O:47])[CH2:43][C:44](O)=[O:45].C(Cl)CCl>CN(C=O)C.CCOC(C)=O>[Si:23]([O:22][CH:20]1[CH2:21][N:18]([C:16]([C:14]2[S:15][C:8]3[C:9](=[N:10][CH:11]=[CH:12][C:7]=3[O:6][C:5]3[CH:30]=[CH:31][C:2]([NH:1][C:44](=[O:45])[CH2:43][C:42]([NH:41][C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=4[O:34][CH3:33])=[O:47])=[CH:3][C:4]=3[F:32])[CH:13]=2)=[O:17])[CH2:19]1)([C:26]([CH3:27])([CH3:28])[CH3:29])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 12664594N-(2-Methoxy-phenyl)-malonamic acidHCID 58790300(7-(4-Amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)methanone

Product 1

HCID 58790105N1-(4-(2-(3-(tert-Butyldimethylsilyloxy)azetidine-1-carbonyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamideYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)methanone 274 (145.2 mg, 0.31 mmol), 27 (77 mg, 0.367 mmol), and EDC (70.3 mg, 0.367 mmol) in DMF (4.4 mL) was stirred overnight at room temperature. The crude mixture was diluted with EtOAc, extracted with water, dried over anhydrous Na2SO4 and concentrated under reduced pressure affording crude 275 (178.4 mg, 0.269 mmol, 87% yield) that was used in the next step without further purification. MS (m/z): (M+1) 665.1 (100%).

Workup

  1. extractionextracted with water
  2. dry with materialdried over anhydrous Na2SO4
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a50a4d03cc034a858a7f84f1eaddec96
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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