Ethylenediamine → 2-[5-difluoromethoxy-1-(1-methyl-1H-pyrazol-4-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246344

Reaction equation

HRID 246344 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[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[N:19]([CH2:30][C:31]4[CH:32]=[N:33][N:34]([CH3:36])[CH:35]=4)[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(N)CN>C(Cl)Cl>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:28])[F:29])[CH:24]=4)[N:19]([CH2:30][C:31]4[CH:32]=[N:33][N:34]([CH3:36])[CH:35]=4)[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712795822-[5-difluoromethoxy-1-(1-methyl-1H-pyrazol-4-ylmethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

Product 1

HCID 712798962-[5-difluoromethoxy-1-(1-methyl-1H-pyrazol-4-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 65.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[5-difluoromethoxy-1-(1-methyl-1H-pyrazol-4-ylmethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (56 mg, 0.09 mmol) in CH2Cl2 (2 mL) was added trifluoroacetic acid (0.5 mL, 6.5 mmol). The reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was dissolved in CH2Cl2 (2 mL) and ethylenediamine (0.2 mL, 2.96 mmol) was added. The reaction mixture was stirred at room temperature for 30 min then quenched with water and extracted with 5% MeOH/CH2Cl2. The organics were dried over MgSO4 and concentrated. The residue was triturated with EtOAc/Et2O and the product was collected via filtration to afford 29 mg (65%) of 2-[5-difluoromethoxy-1-(1-methyl-1H-pyrazol-4-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow solid. MS: (M+Na)+=517; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.62 (br. s., 1H), 8.97 (s, 1H), 8.26 (s, 1H), 8.06 (d, J=1.9 Hz, 1H), 7.85 (d, J=9.1 Hz, 1H), 7.74 (s, 1H), 7.65 (s, 1H), 7.38 (s, 1H), 7.27 (dd, J=9.1, 1.9 Hz, 1H), 7.06 (7, J=75 Hz, 1H), 5.51 (s, 2H), 3.19 (s, 6H), 1.36 (s, 9H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in CH2Cl2 (2 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 30 min
  4. customthen quenched with water
  5. extractionextracted with 5% MeOH/CH2Cl2
  6. dry with materialThe organics were dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was triturated with EtOAc/Et2O
  9. filtrationthe product was collected via filtration

Sources & evidence

ORD record
ord-1a6fcc3aa03c4830b51b3831db26e9a6
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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