1-Hydroxybenzotriazole → HCID 59557927, compound

HRID 221905Notes

Reaction equation

HRID 221905 reaction equation
[C:1]([NH:8][CH2:9][C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C.[NH2:44][CH2:45][C:46]1[CH:51]=[CH:50][C:49]([N:52]2[C:56]([NH:57][C:58]([NH:60][C:61]3[CH:66]=[CH:65][C:64]([O:67][C:68]4[CH:73]=[CH:72][N:71]=[CH:70][CH:69]=4)=[CH:63][CH:62]=3)=[O:59])=[CH:55][C:54]([C:74]([CH3:77])([CH3:76])[CH3:75])=[N:53]2)=[CH:48][CH:47]=1>C1COCC1.C(#N)C>[C:4]([O:3][C:1](=[O:2])[NH:8][CH2:9][C:10](=[O:12])[NH:44][CH2:45][C:46]1[CH:51]=[CH:50][C:49]([N:52]2[C:56]([NH:57][C:58]([NH:60][C:61]3[CH:66]=[CH:65][C:64]([O:67][C:68]4[CH:69]=[CH:70][N:71]=[CH:72][CH:73]=4)=[CH:63][CH:62]=3)=[O:59])=[CH:55][C:54]([C:74]([CH3:77])([CH3:76])[CH3:75])=[N:53]2)=[CH:48][CH:47]=1)([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11554303HCID 11554303, compound

Product 1

HCID 59557927HCID 59557927, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 22177404Acetonitrile tetrahydrofuranSolvent

Procedure

To a solution of N-Boc-glycine (260 mg, 1.48 mmol), EDCl (283 mg, 148 mmol) and HOBT (200 mg, 1.48 mmol) in THF/acetonitrile (50:50, 5 mL) was added N,N-diisopropylethylamine (380 mg, 2.96 mmol), and the resulting reaction mixture was stirred at room temperature for 1 h. Then, 1-[2-(4-aminomethyl-phenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)phenyl]urea (450 mg, 0.99 mmol) was added to the solution and the reaction mixture was stirred at 50° C. for 18 h. The reaction mixture was cooled to room temperature, concentrated at reduced pressure, and the residue was dissolved in EtOAc (20 mL). The solution was washed with water and brine, dried over Na2SO4, and concentrated at reduced pressure. The residue was purified by preparative TLC (50:50 hexanes/EtOAc) to give 65 mg (11%) of the desired product. 1H-NMR (DMSO-d6) δ 8.68 (s, 1H), 8.42 (d, J=6.3 Hz, 2H), 7.98 (s, 1H), 7.82 (b, 1H), 7.61 (d, J=6.9 Hz, 2H), 7.50 (d, J=8.4 Hz, 2H), 7.42 (d, J=8.4 Hz, 2H), 7.08 (d, J=6.6 Hz, 2H), 6.80 (d, J=6.3 Hz, 2H), 6.46 (s, 1H), 4.48 (d, J=6.0 Hz, 2H), 3.78 (d, J=5.7 Hz, 2H), 1.35 (s, 9H), 1.30 (s, 9H); MS LC-MS [M+H]+=614, RT=2.89 min.

Workup

  1. customthe resulting reaction mixture
  2. stirringthe reaction mixture was stirred at 50° C. for 18 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. concentrationconcentrated at reduced pressure
  5. dissolutionthe residue was dissolved in EtOAc (20 mL)
  6. washThe solution was washed with water and brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated at reduced pressure
  9. customThe residue was purified by preparative TLC (50:50 hexanes/EtOAc)

Sources & evidence

ORD record
ord-e3674dee7f3143a79c1868b64ddd2cc8
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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