Imidazole → HCID 89526481, compound

HRID 571392Notes

Reaction equation

HRID 571392 reaction equation
[C:1]([N:20]1[C:28]2[CH:27]=[C:26]([NH2:29])[N:25]=[CH:24][C:23]=2[CH:22]=[N:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1N=CN([C:35]([N:37]2C=N[CH:39]=[CH:38]2)=[O:36])C=1.CCN(C(C)C)C(C)C.N1C=CN=C1.[F:56][C:57]1[CH:62]=[CH:61][C:60]([C@H](N)C)=[CH:59][CH:58]=1>CCOC(C)=O.O1CCOCC1>[F:56][C:57]1[CH:62]=[CH:61][C:60]([C@H:38]([NH:37][C:35]([NH:29][C:26]2[N:25]=[CH:24][C:23]3[CH:22]=[N:21][N:20]([C:1]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[C:28]=3[CH:27]=2)=[O:36])[CH3:39])=[CH:59][CH:58]=1

Participants

8

Reactant 5

HCID 795ImidazoleHCID 682631,1'-Carbonyldiimidazole2×HCID 81531DiisopropylethylamineHCID 6950187(1R)-(+)-1-(4-Fluorophenyl)ethylamineHCID 89525879HCID 89525879, compound

Product 1

HCID 89526481HCID 89526481, compoundYield 28.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine (301 mg, 0.8 mmol), CDI (519 mg, 3.2 mmol), DIEA (0.5 ml, 2.87 mmol and 1,4-dioxane (5 mL) were charged in a microwave vial. The mixture was stirred at 50° C. for 4.5 h. Additional CDI (519 mg, 3.2 mmol) and imidazole (218 mg, 3.20 mmol) were added, the mixture was stirred at 50° C. for 16 h and then treated with (R)-1-(4-fluorophenyl)ethanamine (536 mg, 3.85 mmol). The mixture was stirred at 50° C. for 2 h and then diluted with EtOAc washed with water, brine, dried (Na2SO4) and concentrated in vacuo to afford a residue, which was purified by chromatography on silica gel (0-40% EtOAc in hexane, 25 CV; 40-100% EtOAc in hexane, 20 CV) to afford (R)-1-(1-(4-fluorophenyl)ethyl)-3-(1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (154 mg, 0.229 mmol, 28%) as a yellow solid. MS ESI calc'd. for C34H29FN5O [M+H]+ 542, found 542.

Workup

  1. stirringthe mixture was stirred at 50° C. for 16 h
  2. stirringThe mixture was stirred at 50° C. for 2 h
  3. washwashed with water, brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto afford a residue, which
  7. customwas purified by chromatography on silica gel (0-40% EtOAc in hexane, 25 CV; 40-100% EtOAc in hexane, 20 CV)

Sources & evidence

ORD record
ord-30e3327a32714d45beb2405a4424f22c
Source dataset
uspto-grants-2015_05
Patent number
US09023865B2

Reaction notes

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