1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-[1-(3,3,3-trifluoro-propionyl)-piperidin-3-yl]-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea

HRID 906012Notes

Reaction equation

HRID 906012 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.[NH:12]1[CH2:17][CH2:16][CH2:15][CH:14]([NH:18][C:19]([NH:21][C:22]2[N:23]=[C:24]3[CH:30]=[CH:29][N:28]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:25]3=[N:26][CH:27]=2)=[O:20])[CH2:13]1.[F:39][C:40]([F:46])([F:45])[CH2:41][C:42](O)=[O:43].CCN=C=NCCCN(C)C.C1C=C2N=NN(O)C2=CC=1.O>C(Cl)Cl>[F:39][C:40]([F:46])([F:45])[CH2:41][C:42]([N:12]1[CH2:17][CH2:16][CH2:15][CH:14]([NH:18][C:19]([NH:21][C:22]2[N:23]=[C:24]3[CH:30]=[CH:29][N:28]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:25]3=[N:26][CH:27]=2)=[O:20])[CH2:13]1)=[O:43]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27779723,3,3-Trifluoropropionic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 673855901-piperidin-3-yl-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea dihydrochloride

Product 1

HCID 673859711-[1-(3,3,3-trifluoro-propionyl)-piperidin-3-yl]-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-ureaYield 56.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIPEA (0.082 mL, 0.47 mmol) was added at RT to a mixture of 1-piperidin-3-yl-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea dihydrochloride (0.066 g, 0.142 mmol), 3,3,3-trifluoropropionic acid (0.015 mL, 0.171 mmol), EDCI (0.033 g, 0.171 mmol), HOBt monohydrate (0.026 g, 0.171 mmol) in 1 mL of DCM. The resulting mixture was stirred at RT for 24 hours before being partitioned between H2O and DCM. The aqueous layer was back extracted twice with DCM. The combined organic layers were dried (Na2SO4), filtered, and evaporated. The residue was purified by SiO2 flash chromatography (DCM/(DCM:MeOH:NH4OH 60:10:1] 80% DCM) to give 0.04 g of 1-[1-(3,3,3-trifluoro-propionyl)-piperidin-3-yl]-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea (56% yield).

Workup

  1. custombefore being partitioned between H2O and DCM
  2. extractionThe aqueous layer was back extracted twice with DCM
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by SiO2 flash chromatography (DCM/(DCM:MeOH:NH4OH 60:10:1] 80% DCM)

Sources & evidence

ORD record
ord-a16676eab4574d6db884f6ed2c80d411
Source dataset
uspto-grants-2011_09
Patent number
US08012974B2

Reaction notes

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