4-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-5-amine → 1-[Tri(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridin-5-amine

HRID 1064256Notes

Reaction equation

HRID 1064256 reaction equation
Cl[C:2]1[C:7]([NH2:8])=[CH:6][N:5]=[C:4]2[N:9]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[CH:10]=[CH:11][C:3]=12>C(OCC)(=O)C.C(O)(=O)C.[Zn]>[CH:19]([Si:12]([CH:13]([CH3:15])[CH3:14])([CH:16]([CH3:18])[CH3:17])[N:9]1[C:4]2=[N:5][CH:6]=[C:7]([NH2:8])[CH:2]=[C:3]2[CH:11]=[CH:10]1)([CH3:21])[CH3:20]

Participants

5

Reactant 1

HCID 222736624-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-5-amine

Product 1

HCID 222736141-[Tri(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridin-5-amineYield 70%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (10 g, 32.5 mmol) was dissolved in THF (250 mL) and cooled to −78° C. Sec-Butyllithium ( 54.8 mL, 1.3M/cyclohexane, 71.4 mmol.) was then added dropwise and the solution was stirred for 20 min. A solution of tosylazide (16 g, 81.2 mmol.) in THF (100 mL) was added and the mixture was stirred for 1 h. The reaction mixture was quenched with saturated ammonium chloride (50 mL) and warmed to RT. This mixture was extracted with hexanes (2×200 mL) and the combined organic layers were dried. The organic phase was filtered and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, 100% hexanes) to afford 5-azido-4-chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine as a mixture with starting material (10.2 g). This mixture was directly used in next step. B. 5-Azido-4-chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (1.6 g, 4.6 mmol) was dissolved in ethyl acetate (100 mL) and Pd/C (10%, 100 mg) was added. This suspension was stirred at RT and under 1 atmosphere. of hydrogen for 18 h. The solid was removed by filtration over Celite® and the solution was evaporated in vacuo. The crude product was purified by flash chromatography (silica gel, 95% hexanes, 5% ethyl acetate) to afford 4-chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-ylamine (730 mg, 43.5%, 2 steps). C. 4-Chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-ylamine (10.2 g, 31.5 mmol) was diluted in ethyl acetate (200 mL) and acetic acid (100 mL). Zinc dust (50 g, 0.8 mol.) was added in small portions at RT. After stirring the suspension at RT for 4 h, the mixture was filtered over Celite and the filtrate was slowly neutralized with saturated sodium bicarbonate and extracted with ethyl acetate (2×300 mL). The combined organic layers were dried, filtered and evaporated in vacuo. The crude product was purified by flash chromatography (silica gel, 5% ethyl acetate in hexanes) to afford 1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-ylamine (6.38 g).

Workup

  1. filtrationthe mixture was filtered over Celite
  2. extractionextracted with ethyl acetate (2×300 mL)
  3. customThe combined organic layers were dried
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude product was purified by flash chromatography (silica gel, 5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f91b8e68a360411b85e6bce5c0bf75f9
Source dataset
uspto-grants-2005_11
Patent number
US06969717B2

Reaction notes

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