Dimethylamine → 7-Chloro-2-{4-[(dimethylamino)methyl]phenyl}thieno[3,2-b]pyridine-6-carbonitrile

HRID 1611499Notes

Reaction equation

HRID 1611499 reaction equation
[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[CH:10]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([CH:19]=O)=[CH:15][CH:14]=3)[S:12][C:3]=12.[CH3:21][NH:22][CH3:23].CN(C)C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1.ClCCl.C(O)(=O)C>[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[CH:10]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][N:22]([CH3:23])[CH3:21])=[CH:15][CH:14]=3)[S:12][C:3]=12

Participants

8

Reactant 4

HCID 674DimethylamineHCID 6228DimethylformamideHCID 5049666Sodium triacetoxyborohydrideHCID 114607457-Chloro-2-(4-formylphenyl)thieno[3,2-b]pyridine-6-carbonitrile

Product 1

HCID 111982137-Chloro-2-{4-[(dimethylamino)methyl]phenyl}thieno[3,2-b]pyridine-6-carbonitrileYield 65%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 7-chloro-2-(4-formylphenyl)thieno[3,2-b]pyridine-6-carbonitrile (700 mg, 2.34 mmol) and 6.0 mL of 2.0 M dimethylamine in tetrahydrofuran in 30 mL of dichloromethane and 5 mL of dimethylformamide is cooled to 0-5° C. Sodium triacetoxyborohydride (2.5 g, 11.7 mmol) is added in portions and after 5 minutes 0.10 mL of acetic acid is added. The mixture is stirred at room temperature for 2 hours then quenched by the addition of ice water and partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic phase is dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of dichloromethane to 10% methanol in dichloromethane to provide 496 mg (65%) of 7-chloro-2-{4-[(dimethylamino)methyl]phenyl}thieno[3,2-b]pyridine-6-carbonitrile as a yellow solid, mp 166-168° C.; 1H NMR (DMSO-d6) δ 2.21 (s, 6H), 3.52 (s, 2H), 7.48 (d, J=8 Hz, 2H), 7.95 (d, J=8 Hz, 2H), 8.28 (s, 1H), 9.11 (s, 1H); MS 328.1, 330.1 (M+H)+; HRMS found: 328.06622.

Workup

  1. additionis added
  2. customthen quenched by the addition of ice water
  3. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash column chromatography
  8. washeluting with a gradient of dichloromethane to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-2a4b7f33241946a984fd6e60b358925e
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

Loading…