Sodium bis(trimethylsilyl)amide → 6-Chloro-8-ethyl-thienyl[3',4':6,5]dipyrido[2,3-b:3',2'-f]azepine

HRID 580819Notes

Reaction equation

HRID 580819 reaction equation
Cl[C:2]1[C:7]([C:8]2[C:12]([C:13]3[C:14]([NH:19][CH2:20][CH3:21])=[N:15][CH:16]=[CH:17][CH:18]=3)=[CH:11][S:10][CH:9]=2)=[CH:6][CH:5]=[C:4]([Cl:22])[N:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>O1CCCC1>[CH3:21][CH2:20][N:19]1[C:2]2[N:3]=[C:4]([Cl:22])[CH:5]=[CH:6][C:7]=2[C:8]2[C:12](=[CH:11][S:10][CH:9]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[N:15][C:14]1=2

Participants

4

Reactant 2

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 154085653-(2,6-Dichloropyridin-3-yl)-4-(2-ethylaminopyridin-3-yl)thiophene

Product 1

HCID 4746216-Chloro-8-ethyl-thienyl[3',4':6,5]dipyrido[2,3-b:3',2'-f]azepineYield 45.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-bromo-4-(2-ethylaminopyridin-3-yl)thiophene [synthesis described above] (0.757 g), 2, 6-dichloro-3-tributylstannylpyridine (1.331 g), triphenylarsine (0.261 g), and trisdibenzylideneacetone dipalladium (0.092 g) in N-methylpyrrolidinone (3 mL) was heated at 100° C. for 48 hours. Tetrabutylammonium fluoride (1M in tetrahydrofuran, 3 mL) was added . After 2 hours, the mixture was diluted with ethyl acetate, washed with water, dried, filtered and evaporated. The residue was fractionated by chromatography to give 3-(2,6-dichloropyridin-3-yl)-4-(2-ethylaminopyridin-3-yl)thiophene (0.059 g) which was used directly in the next step. To a solution of 3-(2,6-dichloropyridin-3-yl)-4-(2-ethylaminopyridin-3-yl)thiophene (0.059 g) in tetrahydrofuran (2 mL) was added sodium hexamethyldisilazide (1 molar in tetrahydrofuran, 1 mL). After 20 minutes, the reaction was quenched with methanol, diluted with ethyl acetate, washed with water, dried, filtered and evaporated. The residue was fractionated by chromatography to give 6-chloro-8-ethyl-thienyl[3',4':6,5]dipyrido[2,3-b:3',2'-f]azepine (0.024 g) mp 139-141° C.

Workup

  1. customthe reaction was quenched with methanol
  2. additiondiluted with ethyl acetate
  3. washwashed with water
  4. customdried
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-ac050fff7f5a4974aeec863287118f4d
Source dataset
uspto-grants-1999_07
Patent number
US05919779

Reaction notes

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