6-Bromo-3-pyridinecarboxaldehyde → 6-(7-(2-Fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl)nicotinaldehyde

HRID 2193785Notes

Reaction equation

HRID 2193785 reaction equation
[F:1][C:2]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12](I)[S:13][C:6]=12.Br[C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][N:24]=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:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:23]3[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][N:24]=3)[S:13][C:6]=12

Participants

5

Reactant 2

HCID 117692346-Bromo-3-pyridinecarboxaldehydeHCID 594576617-(2-Fluoro-4-nitrophenoxy)-2-iodothieno[3,2-b]pyridine

Product 1

HCID 594576666-(7-(2-Fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl)nicotinaldehydeYield 52.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 399 (1 g, 2.40 mmol) and 6-bromonicotinaldehyde (450 mg, 2.40 mmol) in 1,4-dioxane (10 mL) was treated sequentially with bis-trimethyl tin (500 μA, 787 mg, 2.40 mmol) and Pd(PPh3)4 (270 mg, 0.24 mmol). The reaction mixture was then heated to reflux under nitrogen overnight, cooled, and concentrated. The crude product was purified by flash chromatography using the gradient 5%-10% MeOH in DCM and subsequent trituration by MeOH, providing pure 400 (494 mg, 52% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.11 (s, 1H), 9.10 (m, 1H), 8.65 (d, 1H, J=5.2 Hz), 8.62 (s, 1H), 8.51 (d, 1H, J=8.8 Hz), 8.48 (dd, 1H, J=2.8 Hz, J=10.4 Hz), 8.38 (dd, 1H, J=2.1 Hz, J=8.2 Hz), 8.20 (m, 1H), 7.73 (t, 1H, J=9.0 Hz), 7.01 (d, 1H, J=5.5 Hz). MS (m/z): (M+1) 395.9.

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureto reflux under nitrogen overnight
  3. temperaturecooled
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-0ba4fc2ef4c44ae28d8f35f9c3ebd9a0
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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