4-Bromopyridin-1-ium-1-olate → 2-(7-(2-Fluoro-4-(3-oxo-3-(phenylamino)propanamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridine 1-oxide

HRID 418738

Reaction equation

HRID 418738 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:19][C:20](=[O:31])[CH2:21][C:22]([NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:23])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.Br[C:33]1[CH:38]=[CH:37][N+:36]([O-:39])=[CH:35][CH:34]=1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:3]=[C:4]([NH:19][C:20](=[O:31])[CH2:21][C:22](=[O:23])[NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:35]3[CH:34]=[CH:33][CH:38]=[CH:37][N+:36]=3[O-:39])[S:17][C:10]=12

Participants

5

Reactant 2

HCID 1397084-Bromopyridin-1-ium-1-olateHCID 58790317N1-(3-Fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamide

Product 1

HCID 587903672-(7-(2-Fluoro-4-(3-oxo-3-(phenylamino)propanamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridine 1-oxideYield 27%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 411 (45 mg, 0.08 mmol), 4-bromopyridine N-oxide (250 mg, 1.43 mmol), bistrimethyltin (26 μL, 40 mg, 0.12 mmol) and Pd(PPh3)4 (10 mg, 0.01 mmol) in dioxane (1 mL) was heated to reflux for 4 hrs. The reaction mixture was cooled, concentrated and the residue was purified by flash chromatography using the gradient 5-10% MeOH in DCM as an eluent, to afford 409 (11 mg, 27% yield). 1H NMR δ (400 MHz, CD3OD): 8.71 (d, 1H, J=5.4 Hz), 8.6 (m, 3H), 8.04 (dd, 1H, J=2.4 Hz, J=12.3 Hz), 7.85 (t, 1H, J=8.4 Hz), 7.78 (m, 2H), 7.65 (m, 1H), 7.62 (m, 1H), 7.53 (m, 3H), 7.32 (t, 1H, J=7.4 Hz), 6.81 (d, 1H, J=5.5 Hz), 3.75 (s, 2H). MS (m/z: (M+1) 515.0 (100%).

Workup

  1. temperatureto reflux for 4 hrs
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated
  4. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-45a326ee1c2b491ab538f92fee0f0834
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Linked notes

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