Carbon tetrabromide → 2-(4-Bromobutyl)-4-[(3,4,5-trimethoxyphenyl)amino]-thieno[2,3-b]pyridine-5-carbonitrile

HRID 1611531Notes

Reaction equation

HRID 1611531 reaction equation
O[CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[S:29][C:9]2=[N:10][CH:11]=[C:12]([C:27]#[N:28])[C:13]([NH:14][C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=3)=[C:8]2[CH:7]=1.C(Br)(Br)(Br)[Br:31].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:31][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[S:29][C:9]2=[N:10][CH:11]=[C:12]([C:27]#[N:28])[C:13]([NH:14][C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=3)=[C:8]2[CH:7]=1

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 10319559HCID 10319559, compound

Product 1

HCID 222566712-(4-Bromobutyl)-4-[(3,4,5-trimethoxyphenyl)amino]-thieno[2,3-b]pyridine-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(4-hydroxybutyl)-4-[(3,4,5-trimethoxyphenyl)amino]-thieno[2,3-b]pyridine-5-carbonitrile (413 mg, 1.0 mmol) and carbon tetrabromide (464 mg, 1.4 mmol) in 10 mL of dichloromethane is added a solution of triphenylphosphine (314 mg, 1.2 mmol) in 5 mL of dichloromethane with stirring. The mixture is stirred at room temperature for 2 hours and concentrated. The residue is purified by flash column chromatography eluting with a gradient of 9:1 hexane:ethyl acetate to 1:2 hexane:ethyl acetate to provide crude 2-(4-bromobutyl)-4-[(3,4,5-trimethoxyphenyl)amino]-thieno[2,3-b]pyridine-5-carbonitrile. The crude 2-(4-bromobutyl)-4-[(3,4,5-trimethoxyphenyl)amino]-thieno[2,3-b]pyridine-5-carbonitrile is heated 70° C. in 2 mL of morpholine in the presence of sodium iodide (100 mg, 0.67 mmol) for 1 hour. The mixture is concentrated, and the residue is purified by flash column chromatography eluting with a gradient of ethyl acetate to 10% methanol in ethyl acetate to provide 2-[4-(4-morpholinyl)butyl]-4-[(3,4,5-trimethoxyphenyl)amino]-thieno[2,3-b]pyridine-5-carbonitrile as a yellow oil; 1H NMR (DMSO-d6) δ 1.49 (quintet, J=7 Hz, 2H), 1.68 (quintet, J=7 Hz, 2H), 2.31 (m, 6H), 2.87 (t, J=7 Hz, 2H), 3.55 (m, 4H), 3.67 (s, 3H), 3.74 (s, 6H), 6.59 (s, 2H), 7.23 (s, 1H), 8.37 (s, 1H), 9.46 (s, 1H); MS 483.5 (M+H)+.

Workup

  1. stirringThe mixture is stirred at room temperature for 2 hours
  2. concentrationconcentrated
  3. customThe residue is purified by flash column chromatography
  4. washeluting with a gradient of 9:1 hexane

Sources & evidence

ORD record
ord-7be7e2a9e30f41d3b8290a57fcf46860
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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