Hydrochloric Acid → 1-(4-(4-Amino-1h-pyrrolo[3,2-c]pyridin-3-yl)phenyl)-3-(2-(4-fluorophenyl)acetyl)urea, hydrochloride salt

HRID 230762Notes

Reaction equation

HRID 230762 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]=[C:12]=[O:13])=[O:10])=[CH:4][CH:3]=1.[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:25]3[C:26]([NH2:30])=[N:27][CH:28]=[CH:29][C:24]=3[NH:23][CH:22]=2)=[CH:17][CH:16]=1.[ClH:31].O1CCOCC1>C(Cl)Cl.CC#N>[ClH:31].[NH2:30][C:26]1[C:25]2[C:21]([C:18]3[CH:19]=[CH:20][C:15]([NH:14][C:12]([NH:11][C:9](=[O:10])[CH2:8][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[O:13])=[CH:16][CH:17]=3)=[CH:22][NH:23][C:24]=2[CH:29]=[CH:28][N:27]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 231530882-(4-Fluorophenyl)acetyl isocyanate2×HCID 577631573-(4-Aminophenyl)-1h-pyrrolo[3,2-c]pyridin-4-amine

Product 1

HCID 116907221-(4-(4-Amino-1h-pyrrolo[3,2-c]pyridin-3-yl)phenyl)-3-(2-(4-fluorophenyl)acetyl)urea, hydrochloride saltYield 50%

Reagents, catalysts & solvents 1

HCID 21877088Acetonitrile methylene chlorideSolvent

Procedure

2-(4-Fluorophenyl)acetyl isocyanate (Compound C of Example 3, 0.29 M, 0.062 mL, 0.018 mmol, 2.0 eq) was added to a solution of 3-(4-aminophenyl)-1H-pyrrolo[3,2-c]pyridin-4-amine (0.002 g, 0.009 mmol, 1.0 eq) in 1/1 DCM/CH3CN (1 mL) and the reaction mixture was stirred at room temperature for 6 h. The reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography (SiO2, eluting 0-5% MeOH in CHCl3). The appropriate fractions were isolated and concentrated in vacuo. The residue was dissolved in THF (1 mL), cooled to 0° C. and treated with anhydrous 4 N HCl in dioxane (1 mL, 4.0 mmol, 168 eq). The reaction mixture was stirred at 0° C. for 1 h and the resulting heterogeneous solution was concentrated in vacuo. The residue was triturated with Et2O, discarding the filtrate and the solid dried in vacuo to afford the title compound (0.002 g, 50%) as a pale yellow solid. MS(ESI+) m/z 404 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was purified by flash chromatography (SiO2, eluting 0-5% MeOH in CHCl3)
  3. customThe appropriate fractions were isolated
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in THF (1 mL)
  6. temperaturecooled to 0° C.
  7. stirringThe reaction mixture was stirred at 0° C. for 1 h
  8. concentrationthe resulting heterogeneous solution was concentrated in vacuo
  9. customThe residue was triturated with Et2O
  10. customthe solid dried in vacuo

Sources & evidence

ORD record
ord-b3c1f44302cc49c2bf95cb2355217b8d
Source dataset
uspto-grants-2009_07
Patent number
US07566784B2

Reaction notes

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