Imidazole → HCID 73505653, compound

HRID 590869Notes

Reaction equation

HRID 590869 reaction equation
N1[CH:5]=[CH:4]N=C1.C(OC(=O)[N:12]([C:15]1[C:19]2[CH:20]=[N:21][C:22]([NH2:24])=[CH:23][C:18]=2[N:17](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:16]=1)[CH2:13][CH3:14])(C)(C)C.[C:45]([N:52]1[CH:56]=[CH:55][N:54]=[CH:53]1)(N1C=CN=C1)=[O:46].CCN(C(C)C)[CH:60]([CH3:62])[CH3:61].C([SiH](CC)CC)C>C(Cl)Cl.CN(C=O)C>[CH2:13]([NH:12][C:15]1[C:19]2[CH:20]=[N:21][C:22]([NH:24][C:45]([NH:52][CH:56]([C:55]3[CH:62]=[CH:60][CH:61]=[CH:53][N:54]=3)[CH2:4][CH3:5])=[O:46])=[CH:23][C:18]=2[NH:17][N:16]=1)[CH3:14]

Participants

8

Reactant 5

HCID 795ImidazoleHCID 12052TriethylsilaneHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 118390790HCID 118390790, compound

Product 1

HCID 73505653HCID 73505653, compoundYield 23.69%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a 8 mL vial charged with imidazole (17.3 mg, 0.26 mmol) and tert-butyl(6-amino-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)(ethyl)carbamate (26.5 mg, 0.051 mmol) in DCM (1 ml) was added 1,1′-carbonyldiimidazole (25 mg, 0.153 mmol). The reaction mixture was stirred at room temperature for 5 h, leading to a clear yellow solution. A solution of 1-(pyridin-2-yl)propan-1-amine, 2HC1 (21.33 mg, 0.102 mmol) and DIEA (0.045 ml, 0.255 mmol) in DMF (1 ml) was added. The vial was capped and the contents stirred at room temperature for 16 h. The reaction mixture was concentrated and the resulting residue re-dissolved in TFA (1 ml) and stirred at room temperature for 20 minutes. Triethylsilane (0.008 ml, 0.051 mmol) was added drop wise, and the reaction mixture stirred for an additional 5 minutes. The mixture was concentrated, re-dissolved in DMSO (1.5 mL) and submitted for purification by mass-triggered preparative HPLC to afford 1-(3-(ethylamino)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-(pyridin-2-yl)propyl)urea (4.1 mg, 0.012 mmol, 23.69% yield) as a white solid. MS ESI calc'd. For C17H21N7O [M+H]+ 340. found 340. 1H NMR (ppm, 600 MHz, DMSO): δ 8.99 (s, 1H); 8.57 (s, 1H); 8.52 (d, J=4.8 Hz, 1H); 7.73 (td, J=7.7, 1.8 Hz, 1H); 7.31 (d, J=7.8 Hz, 1H); 7.21-7.24 (m, 2H); 4.76 (q, J=7.2 Hz, 1H); 3.19-3.23 (m, 2H); 1.77-1.82 (m, 1H); 1.69-1.74 (m, 1H); 1.17 (t, J=7.2 Hz, 3H); 0.80 (t, J=7.4 Hz, 3H).

Workup

  1. customThe vial was capped
  2. stirringthe contents stirred at room temperature for 16 h
  3. concentrationThe reaction mixture was concentrated
  4. dissolutionthe resulting residue re-dissolved in TFA (1 ml)
  5. stirringstirred at room temperature for 20 minutes
  6. stirringthe reaction mixture stirred for an additional 5 minutes
  7. concentrationThe mixture was concentrated
  8. dissolutionre-dissolved in DMSO (1.5 mL)
  9. customsubmitted for purification by mass-triggered preparative HPLC

Sources & evidence

ORD record
ord-9be4cdcd3d294e8ab81b51f3b8e7d851
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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