Acetic Acid → 1-[2-[3-(5,6-Dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-ylmethyl)-phenyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one

HRID 1677415Notes

Reaction equation

HRID 1677415 reaction equation
[CH3:1][C:2]([CH3:31])([CH3:30])[C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([C:14]3[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=3)[CH:17]=O)[N:12]=2)[N:7]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:6]=1)=[O:4].[N:32]1[N:33]=[CH:34][N:35]2[CH2:40][CH2:39][NH:38][CH2:37][C:36]=12.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[N:32]1[N:33]=[CH:34][N:35]2[CH2:40][CH2:39][N:38]([CH2:17][C:16]3[CH:15]=[C:14]([C:11]4[N:12]=[C:13]5[C:5]([C:3](=[O:4])[C:2]([CH3:1])([CH3:31])[CH3:30])=[CH:6][N:7]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:28])([CH3:29])[CH3:27])[C:8]5=[N:9][CH:10]=4)[CH:21]=[CH:20][CH:19]=3)[CH2:37][C:36]=12

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 179987185H,6H,7H,8H-(1,2,4)triazolo(4,3-a)pyrazineHCID 866466863-[7-(2,2-Dimethyl-propionyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-benzaldehyde

Product 1

HCID 673464281-[2-[3-(5,6-Dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-ylmethyl)-phenyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-oneYield 40%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 3-[7-(2,2-Dimethyl-propionyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-benzaldehyde (0.150 g, 0.3428 mmol) and 5,6,7,8-Tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (0.064 g, 0.514 mmol) in 1.2 mL of dichloroethane was added 1.2 mL acetic acid and 0.109 g of sodium triacetoxyborohydride (0.514 mmol). The reaction was stirred overnight at room temperature before quenching with saturated aqueous Na2CO3. The reaction mixture was extracted 3 times with ethyl acetate, combined organics dried over MgSO4, filtered and concentrated in vacuo. Silica gel chromatography (0→100% EtOAc/hexanes over 30 minutes, followed by a flush with 100% methanol) afforded 0.0744 g (40% yield) of 1-[2-[3-(5,6-Dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-ylmethyl)-phenyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one as a white solid. MS (E/I): 546 (M+H)

Workup

  1. custombefore quenching with saturated aqueous Na2CO3
  2. extractionThe reaction mixture was extracted 3 times with ethyl acetate
  3. dry with materialcombined organics dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. waitSilica gel chromatography (0→100% EtOAc/hexanes over 30 minutes
  7. customa flush with 100% methanol)

Sources & evidence

ORD record
ord-820600cf55e44dd59aa557b00838b53b
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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