Water → HCID 123714628, compound

HRID 1509118Notes

Reaction equation

HRID 1509118 reaction equation
[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:26][C:25]4[C:24](=[N:34][NH2:35])[NH:23][CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.O.[CH3:59][N:60]1[CH:64]=[C:63]([C:65](O)=O)[N:62]=[CH:61]1>CN(C=O)C>[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:27]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:26][C:25]4[C:24]5=[N:34][N:35]=[C:65]([C:63]6[N:62]=[CH:61][N:60]([CH3:59])[CH:64]=6)[N:23]5[CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 962WaterHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 5415091-methyl-1H-imidazole-4-carboxylic acidHCID 178452592HCID 178452592, compound

Product 1

HCID 123714628HCID 123714628, compoundYield 5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl(1-(4-(5-hydrazono-3-phenyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)phenyl)cyclobutyl)carbamate (22 mg, 0.04 mmol) in dry DMF (1 mL) was added EDCI (11 mg, 0.06 mmol), HOBt.H2O (8 mg, 0.06 mmol) and 1-methyl-1H-imidazole-4-carboxylic acid (8 mg, 0.06 mmol) under nitrogen. The reaction mixture was heated at 60° C. overnight. After cooled down to room temperature, the mixture was partitioned between saturated NaHCO3 solution and ethyl acetate. The layers were separated and the organic phase washed with water and brine, dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The resulting residue was purified by preparative HPLC (method G, gradient 5 to 95% 0.1% FA/ACN in 0.1% FA/H2O) to give the title compound (1 mg, 5%). 1H NMR (500 MHz, CDCl3): 8.49 (1H, s), 7.74 (1H, s), 7.54 (1H, s), 7.38 (2H, d), 7.31 (2H, d), 7.28-7.23 (5H, m), 5.01 (1H, br s), 4.94 (2H, t), 3.81 (3H, s), 3.49 (2H, t), 2.60-2.30 (4H, m), 2.10-2.01 (1H, m), 1.85-1.76 (1H, m), 1.45-1.20 (9H, br).

Workup

  1. temperatureAfter cooled down to room temperature
  2. customthe mixture was partitioned between saturated NaHCO3 solution and ethyl acetate
  3. customThe layers were separated
  4. washthe organic phase washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe resulting residue was purified by preparative HPLC (method G, gradient 5 to 95% 0.1% FA/ACN in 0.1% FA/H2O)

Sources & evidence

ORD record
ord-c65b61b9a1ec49be8f4f6847e1bd8cdc
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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