HCID 22256626, compound → HCID 22256645, compound

HRID 1611554Notes

Reaction equation

HRID 1611554 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[N:2]1.O.[OH-].[Cs+].[Cl:9][C:10]1[CH:15]=[C:14]([Cl:16])[C:13]([O:17][CH3:18])=[CH:12][C:11]=1[NH:19][C:20]1[C:25]([C:26]#[N:27])=[CH:24][N:23]=[C:22]2[CH:28]=[C:29]([C:31]#[CH:32])[S:30][C:21]=12>CN1CCCC1=O>[Cl:9][C:10]1[CH:15]=[C:14]([Cl:16])[C:13]([O:17][CH3:18])=[CH:12][C:11]=1[NH:19][C:20]1[C:25]([C:26]#[N:27])=[CH:24][N:23]=[C:22]2[CH:28]=[C:29](/[CH:31]=[CH:32]/[N:2]3[N:3]=[CH:4][CH:5]=[N:1]3)[S:30][C:21]=12

Participants

5

Reactant 3

HCID 22256626HCID 22256626, compoundHCID 23679066Caesium hydroxide--water (1/1/1)HCID 178418936HCID 178418936, compound

Product 1

HCID 22256645HCID 22256645, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 1,2,3-triazole (50 μL, 0.81 mmol) and cesium hydroxide monohydrate (18 mg, 0.11 mmol) in 1-methyl-2-pyrrolidinone (5 mL) is added slowly 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-ethynylthieno[3,2-b]pyridine-6-carbonitrile (200 mg, 0.54 mmol). The mixture is heated to 120° C. for 12 hours, cooled to room temperature and partitioned between water and ethyl acetate. The organic layer is washed with water, dried over sodium sulfate, and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of methanol in dichloromethane (0-2%) to provide 90 mg (38%) of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[(E)-2-(2H-1,2,3-triazol-2-yl)vinyl]thieno[3,2-b]pyridine-6-carbonitrile as a yellow solid, mp 315-316° C.; 1H NMR (DMSO-d6−TFA) δ 3.88 (s, 3H), 7.50 (s, 1H), 7.65 (d, J=14 Hz, 1H), 7.85 (s, 1H), 7.88 (s, 1H), 8.15 (s, 2H), 8.32 (d, J=14 Hz, 1H), 9.01 (s, 1H); MS 443.0 (M+H)+.

Workup

  1. temperaturecooled to room temperature
  2. custompartitioned between water and ethyl acetate
  3. washThe organic layer is washed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by flash column chromatography
  7. washeluting with a gradient of methanol in dichloromethane (0-2%)

Sources & evidence

ORD record
ord-92555ca2c71a4717b7d546f9c453063b
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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