Triethylamine → 7-Chloro-2-(pyrrolidin-1-ylmethyl)thieno[3,2-b]pyridine

HRID 985317Notes

Reaction equation

HRID 985317 reaction equation
O[CH2:2][C:3]1[S:11][C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[Cl:12])[CH:4]=1.[CH2:13]([N:15](CC)[CH2:16][CH3:17])[CH3:14].S(Cl)(C)(=O)=O.N1CCCC1.C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=O.[Mg+2]>ClC(Cl)C.[Cl-].[Na+].O.ClCCl>[Cl:12][C:9]1[CH:8]=[CH:7][N:6]=[C:5]2[CH:4]=[C:3]([CH2:2][N:15]3[CH2:16][CH2:17][CH2:14][CH2:13]3)[S:11][C:10]=12

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 31268PyrrolidineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 22143534(7-Chlorothieno[3,2-b]pyridin-2-yl)methanol

Product 1

HCID 221435927-Chloro-2-(pyrrolidin-1-ylmethyl)thieno[3,2-b]pyridineYield 56.2%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 2-(hydroxymethyl)-7-chlorothieno[3,2-b]pyridine 114a (100 mg, 0.5 mmole) in dichloroethane was treated with triethylamine (0.08 mL, 0.55 mmole) and mesyl chloride (0.04 mL, 0.55 mmole). The clear solution was stirred for 30 minutes and treated with pyrrolidine (0.12 mL, 1.5 mmole). After one hour, the reaction mixture was poured into 5% sodium bicarbonate and the workup was performed with dichloromethane, brine and magnesium sulfate. The crude product (167 mg greenish oil) was purified over silica gel (1 mm plate) using 2% methanol-chloroform with 0.1% ammonium hydroxide, which provided the title compound as a clear oil (71 mg, 56%): 1H-NMR (DMSO-d6, 400 MHz) δ8.58 (1H, d, J=5.1 Hz), 7.51-7.49 (2H, m), 3.96 (2H, s), 2.56 (4H, bs), 1.75-1.72 (4H, m); MS m/z 253 (M+H)+.

Workup

  1. waitAfter one hour
  2. customThe crude product (167 mg greenish oil) was purified over silica gel (1 mm plate)

Sources & evidence

ORD record
ord-792e8c3fb27842f89868381e16ab9e49
Source dataset
uspto-grants-2005_03
Patent number
US06869962B2

Reaction notes

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