Acetyl chloride → Acetamide, N-[1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-B]pyridin-5-YL]-

HRID 1064260Notes

Reaction equation

HRID 1064260 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[CH:5]([Si:8]([CH:22]([CH3:24])[CH3:23])([CH:19]([CH3:21])[CH3:20])[N:9]1[C:13]2=[N:14][CH:15]=[C:16]([NH2:18])[CH:17]=[C:12]2[CH:11]=[CH:10]1)([CH3:7])[CH3:6].[Cl-].[NH4+].C(OCC)(=O)C>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[CH:22]([Si:8]([CH:5]([CH3:7])[CH3:6])([CH:19]([CH3:21])[CH3:20])[N:9]1[C:13]2=[N:14][CH:15]=[C:16]([NH:18][C:1](=[O:3])[CH3:2])[CH:17]=[C:12]2[CH:11]=[CH:10]1)([CH3:24])[CH3:23]

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 222736141-[Tri(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridin-5-amine

Product 1

HCID 22273659Acetamide, N-[1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-B]pyridin-5-YL]-Yield 53%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

Acetyl chloride (75 μL, 1.0 mmol) was added to a solution of 1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-ylamine (230 mg, 0.8 mmol) and 4-dimethylaminopyridine (5 mg) in pyridine (1.6 mL). The mixture was stirred at RT for 24 h and a saturated solution of ammonium chloride (30 mL) and ethyl acetate (30 mL) were added. The separated aqueous layer was extracted with ethyl acetate (3×25 mL) and the combined organic layers were dried, filtered and concentrated to provide an oil which was purified by preparative HPLC to afford N-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-acetamide (140 mg, 53%) as an oil: LCMS; m/z 332 (M+H+). B. At RT under argon, a solution of borane-dimethylsulfide complex (665 μL, 6.6 mmol, 10 M) was added to N-methyl-N-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-acetamide (110 mg, 0.33 mmol) in THF (3.0 mL). The mixture was heated to 65° C. for 2 h., cooled down and a 6N hydrochloric acid solution was slowly added. The mixture was heated to 100° C. and vigorously stirred for 12 h., cooled down and a 6 N sodium hydroxide solution was added until pH 7 was reached. The mixture was extracted with ethyl acetate (3×15 mL) and the combined organic layers were dried, filtered and evaporated to provide an oil which was purified through silica gel-SCX column (arylsulfonic acid with washes with methanol and 2N NH3 in methanol) to afford ethyl-(1H-pyrrolo[2,3-b]pyridin-5-yl)-amine. LCMS; m/z 203 (M+AcCN), 162 (M+H)+.

Workup

  1. extractionThe separated aqueous layer was extracted with ethyl acetate (3×25 mL)
  2. customthe combined organic layers were dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto provide an oil which
  6. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-bc7c9ed192734855a790633b1ff28620
Source dataset
uspto-grants-2005_11
Patent number
US06969717B2

Reaction notes

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