2-imidazo[1,5-a]pyridin-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide → N-Tert-Butyl-2-(5,6,7,8-Tetrahydroimidazo[1,5-A]pyridin-1-Yl)-5h-Pyrrolo[2,3-B]pyrazine-7-Carboxamide

HRID 246348Notes

Reaction equation

HRID 246348 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[N:18]=[CH:19][N:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=34)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)(C(F)(F)F)=O.[Pt](=O)=O>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[N:18]=[CH:19][N:20]4[CH2:25][CH2:24][CH2:23][CH2:22][C:21]=34)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 712796032-imidazo[1,5-a]pyridin-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

Product 1

HCID 71280008N-Tert-Butyl-2-(5,6,7,8-Tetrahydroimidazo[1,5-A]pyridin-1-Yl)-5h-Pyrrolo[2,3-B]pyrazine-7-CarboxamideYield 26%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 2-imidazo[1,5-a]pyridin-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (70 mg, 0.15 mmol) in TFA (2 mL) was added platinum(IV) oxide (7 mg, 0.03 mmol). The reaction mixture was stirred under hydrogen (balloon) for 6 h then filtered over Celite, rinsing with CH2Cl2. The filtrate was concentrated. The residue was dissolved in CH2Cl2 (3 mL) and treated with ethylenediamine (0.4 mL). The reaction mixture was stirred for 1 h then quenched with water and extracted with CH2Cl2 (2×). The combined organics were dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 0% to 3% MeOH/CH2Cl2 (0.5% NH4OH). The appropriate fractions were combined and concentrated to afford a yellow solid which was triturated with Et2O to obtain 13 mg (26%) of 2-(5,6,7,8-tetrahydro-imidazo[1,5-a]pyridin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a pale yellow solid. MS: (M+H)+=339; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.50 (br. s., 1H), 8.96 (s, 1H), 8.21 (s, 1H), 7.75 (s, 1H), 7.66 (s, 1H), 4.06 (t, J=5.9 Hz, 2H), 3.21 (t, J=6.2 Hz, 2H), 1.76-1.98 (m, 4H), 1.46 (s, 9H).

Workup

  1. filtrationthen filtered over Celite
  2. washrinsing with CH2Cl2
  3. concentrationThe filtrate was concentrated
  4. dissolutionThe residue was dissolved in CH2Cl2 (3 mL)
  5. additiontreated with ethylenediamine (0.4 mL)
  6. stirringThe reaction mixture was stirred for 1 h
  7. customthen quenched with water
  8. extractionextracted with CH2Cl2 (2×)
  9. dry with materialThe combined organics were dried over MgSO4
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel chromatography with 0% to 3% MeOH/CH2Cl2 (0.5% NH4OH)
  12. concentrationconcentrated
  13. customto afford a yellow solid which
  14. customwas triturated with Et2O

Sources & evidence

ORD record
ord-432aa5120fd64af98c799dc42ba05eed
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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