1,2-Dichloroethane → N1-(3-Fluoro-4-(2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(2-methoxyphenyl)malonamide

HRID 2193696Notes

Reaction equation

HRID 2193696 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10](=[O:15])[CH2:11][C:12]([OH:14])=O.C1C=CC2N(O)N=NC=2C=1.[F:26][C:27]1[CH:28]=[C:29]([NH2:56])[CH:30]=[CH:31][C:32]=1[O:33][C:34]1[CH:39]=[CH:38][N:37]=[C:36]2[CH:40]=[C:41]([C:43]3[N:44]=[CH:45][N:46]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:55])([CH3:54])[CH3:53])[CH:47]=3)[S:42][C:35]=12.C(Cl)CCl>CN(C=O)C>[F:26][C:27]1[CH:28]=[C:29]([NH:56][C:12](=[O:14])[CH2:11][C:10]([NH:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])=[O:15])[CH:30]=[CH:31][C:32]=1[O:33][C:34]1[CH:39]=[CH:38][N:37]=[C:36]2[CH:40]=[C:41]([C:43]3[N:44]=[CH:45][N:46]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:54])([CH3:53])[CH3:55])[CH:47]=3)[S:42][C:35]=12

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 12664594N-(2-Methoxy-phenyl)-malonamic acidHCID 587902083-fluoro-4-(2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)benzenamine

Product 1

HCID 58790420N1-(3-Fluoro-4-(2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(2-methoxyphenyl)malonamideYield 58.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the acid 27 (59 mg, 2 eq, 0.28 mmol) and HOBT (19 mg, 1 eq, 0.14 mmol) in DMF (3 ml) was added amine 104 (64 mg, 0.14 mmol) and the reaction mixture was stirred for 10 mins. EDC (54 mg, 2 eq, 0.28 mmol) was added and the reaction mixture was stirred at RT overnight. The solvents were removed and the residue was partitioned between EtOAc and water. The organic phase was collected, dried over anhydrous sodium sulfate, filtered and concentrated. Purification by column chromatography (20% acetone in hexane to 100% acetone) afforded title compound 105 (53 mg, 58% yield). MS (m/z): 648.2 (M+H).

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. customThe solvents were removed
  3. customthe residue was partitioned between EtOAc and water
  4. customThe organic phase was collected
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography (20% acetone in hexane to 100% acetone)

Sources & evidence

ORD record
ord-8b9c46cf086744cd861373c7d1bf1dc5
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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