Ethylenediamine → 2-(1-methyl-1,4,5,6,7,8-hexahydrocycloheptapyrazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246336

Reaction equation

HRID 246336 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:21]4[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:20]=4[N:19]([CH3:27])[N:18]=3)[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.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:21]4[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:20]=4[N:19]([CH3:27])[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 712794412-(1-methyl-1,4,5,6,7,8-hexahydrocycloheptapyrazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

Product 1

HCID 712797352-(1-methyl-1,4,5,6,7,8-hexahydrocycloheptapyrazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 68.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(1-methyl-1,4,5,6,7,8-hexahydrocycloheptapyrazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (40 mg, 0.08 mmol) in CH2Cl2 (2 mL) was added TFA (1.0 mL, 13.0 mmol). The yellow reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was redissolved in CH2Cl2 (2 mL) and ethylenediamine (0.1 mL, 1.48 mmol) was added. The reaction mixture was stirred at room temperature for 0.5 h then concentrated and directly purified by silica gel chromatography with 0% to 3% MeOH/EtOAc to isolate 20 mg (68%) of 2-(1-methyl-1,4,5,6,7,8-hexahydrocycloheptapyrazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as an off-white solid. MS: (M+Na)+=389; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.63 (br. s., 1H), 8.80 (s, 1H), 8.27 (s, 1H), 7.83 (s, 1H), 3.81 (s, 3H), 3.02-3.12 (m, 2H), 2.74-2.83 (m, 2H), 1.82 (br. s., 2H), 1.57-1.73 (m, 4H), 1.44 (s, 9H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in CH2Cl2 (2 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 0.5 h
  4. concentrationthen concentrated
  5. customdirectly purified by silica gel chromatography with 0% to 3% MeOH/EtOAc

Sources & evidence

ORD record
ord-590931cd81ef4f5fac9084b27ac0b417
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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