Triethylsilane → methyl 3-[(1H-Pyrrolo[2,3-b]pyridin-4-ylmethyl)amino]thiophene-2-carboxylate

HRID 641800Notes

Reaction equation

HRID 641800 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][CH:7]=[CH:8][C:9]=1[NH2:10])=[O:4].[NH:11]1[C:15]2[N:16]=[CH:17][CH:18]=[C:19]([CH:20]=O)[C:14]=2[CH:13]=[CH:12]1.C([SiH](CC)CC)C.[OH-].[Na+].C([O-])(O)=O.[Na+]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH:11]1[C:15]2=[N:16][CH:17]=[CH:18][C:19]([CH2:20][NH:10][C:9]3[CH:8]=[CH:7][S:6][C:5]=3[C:3]([O:2][CH3:1])=[O:4])=[C:14]2[CH:13]=[CH:12]1

Participants

7

Reactant 5

HCID 12052TriethylsilaneHCID 14798Sodium HydroxideHCID 89652Methyl 3-amino-2-thiophenecarboxylateHCID 516892Sodium BicarbonateHCID 219638871H-Pyrrolo[2,3-b]pyridine-4-carbaldehyde

Product 1

HCID 21963881methyl 3-[(1H-Pyrrolo[2,3-b]pyridin-4-ylmethyl)amino]thiophene-2-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-aminothiophene-2-carboxylic acid methyl ester (110 mg, 0.701 mmol), and 1H-Pyrrolo[2,3-b]pyridine-4-carboxaldehyde (107 mg, 0.736 mmol) in TFA/CH2Cl2 (2 mL/2 mL) was stirred at 50° C. for 3 hr. The solution was cooled to 0° C. and triethylsilane (0.224 mL, 1.40 mmol) was added dropwise. The mixture was then stirred at 50° C. for 4 hr and treated with 2 N NaOH (aq)(to pH 6) and then saturated NaHCO3 (aq)(to pH 8). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (3×10 mL). The organic extracts were combined, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by chromatography over silica gel (gradient of 20% EtOAc/Hexanes to 70% EtOAc/Hexanes) to yield methyl 3-[(1H-Pyrrolo[2,3-b]pyridin-4-ylmethyl)amino]thiophene-2-carboxylate (98 mg, 49%). MS (ES+): 287 [MH+]. 1H NMR (DMSO-d6, 400 MHz): δ 3.75 (s, 3H), 4.84 (d, 2H, J=4.4 Hz), 6.74 (dd, 1H, J=2.8 Hz & 2.0 Hz), 6.70 (d, 1H, J=5.6 Hz), 7.01 (d, 1H, J=4.8 Hz), 7.51 (t, 1H, J=2.4 Hz), 7.61 (d, 1H, J=5.2 Hz), 8.18 (d, 1H, J=4.8 Hz),

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with CH2Cl2 (3×10 mL)
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography over silica gel (gradient of 20% EtOAc/Hexanes to 70% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-50f3877c462b46dbbf072633e7160fb4
Source dataset
uspto-grants-2010_04
Patent number
US07696225B2

Reaction notes

Loading…