Acetyl chloride → (R)-N-ethyl-N-(6-(3-(1-phenylethyl)ureido)-1H-pyrazolo[4,3-c]pyridin-3-yl)acetamide

HRID 590808Notes

Reaction equation

HRID 590808 reaction equation
[CH2:1]([NH:3][C:4]1[C:8]2[CH:9]=[N:10][C:11]([NH:13][C:14]([NH:16][C@@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])=[O:15])=[CH:12][C:7]=2[N:6](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:5]=1)[CH3:2].CCN(C(C)C)C(C)C.[C:53](Cl)(=[O:55])[CH3:54].C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C>C(Cl)Cl>[CH2:1]([N:3]([C:4]1[C:8]2[CH:9]=[N:10][C:11]([NH:13][C:14]([NH:16][C@@H:17]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH3:18])=[O:15])=[CH:12][C:7]=2[NH:6][N:5]=1)[C:53](=[O:55])[CH3:54])[CH3:2]

Participants

7

Reactant 5

HCID 6367Acetyl chlorideHCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 81531DiisopropylethylamineHCID 118272409(R)-1-(3-(ethylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Product 1

HCID 118272482(R)-N-ethyl-N-(6-(3-(1-phenylethyl)ureido)-1H-pyrazolo[4,3-c]pyridin-3-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(R)-1-(3-(Ethylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (Example 2, Step 2; 680 mg, 1.198 mmol) was dissolved in DCM (20 mL), charged with DIEA (0.42 mL, 2.396 mmol), and cooled to 0° C. Acetyl chloride (0.095 mL, 1.318 mmol) was added drop-wise and the reaction was warmed to room temperature and stirred for 1 h. The reaction was charged with TFA (2.3 mL, 30.0 mmol) and triethylsilane (0.20 mL, 1.198 mmol) and stirred for 1 h at room temperature. The solvents were removed in vacuo and the residue was treated with DCM (3 mL) and triethylamine (1 mL) and stirred for 15 min. The residue was purified by flash chromatography (2-10% MeOH/DCM w/NH3) to afford (R)—N-ethyl-N-(6-(3-(1-phenylethyl)ureido)-1H-pyrazolo[4,3-c]pyridin-3-yl)acetamide. MS ESI calc'd. for C19H22N6O2 [M+1]+ 366. found 366.

Workup

  1. temperaturethe reaction was warmed to room temperature
  2. stirringstirred for 1 h at room temperature
  3. customThe solvents were removed in vacuo
  4. additionthe residue was treated with DCM (3 mL) and triethylamine (1 mL)
  5. stirringstirred for 15 min
  6. customThe residue was purified by flash chromatography (2-10% MeOH/DCM w/NH3)

Sources & evidence

ORD record
ord-e0ac328995a44fd09aeeddcfba1e319e
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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