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

HRID 418625Notes

Reaction equation

HRID 418625 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[N:20]=[CH:21][N:22]([CH2:24][O:25][CH3:26])[CH:23]=3)[S:18][C:11]=12)[NH2:5].[CH3:27][O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[NH:35][C:36](=[O:41])[CH2:37][C:38](O)=[O:39].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:38](=[O:39])[CH2:37][C:36]([NH:35][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[O:28][CH3:27])=[O:41])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[N:20]=[CH:21][N:22]([CH2:24][O:25][CH3:26])[CH:23]=3)[S:18][C:11]=12

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 12664594N-(2-Methoxy-phenyl)-malonamic acidHCID 587902243-fluoro-4-(2-(1-(methoxymethyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)aniline

Product 1

HCID 16041775N1-(3-Fluoro-4-(2-(1-(methoxymethyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(2-methoxyphenyl)malonamideYield 72.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 95 (136 mg, 0.37 mmol) in dry DMF (7 ml) was added the acid 27 (300 mg, 3.0 eq, 1.1 mmol), HOBT (74 mg, 1.5 eq, 0.55 mmol) and EDC (210 mg, 3.0 eq, 1.1 mmol) and the reaction mixture was stirred at RT overnight. The reaction mixture was concentrated to dryness and partitioned between EtOAc and sat NaHCO3 soln, the organic phase was collected, dried over anhydrous sodium sulfate and filtered. The solvent was removed under reduced pressure and the crude was triturated with Et2O to afford title compound 92 (150 mg, 72% yield). 1H NMR (DMSO-d6) δ(ppm): 10.57 (s, 1H), 9.62 (s, 1H), 8.43 (d, J=5.48 Hz, 1H), 8.06 (m, 2H), 7.93 (m, 1H), 7.85 (m, 1H), 7.76 (s, 1H), 7.45 (m, 2H), 7.05 (m, 2H), 6.90 (m, 1H), 6.58 (m, 1H), 5.35 (s, 2H), 3.84 (m, 3H), 3.63 (s, 2H), 3.25 (s, 3H). MS (m/z): 562.1 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. custompartitioned between EtOAc
  3. customthe organic phase was collected
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customThe solvent was removed under reduced pressure
  7. customthe crude was triturated with Et2O

Sources & evidence

ORD record
ord-55da49e1e71345338b990a2de4e88c0d
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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