1-Hydroxybenzotriazole → (S)-N-{1-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamide

HRID 872796Notes

Reaction equation

HRID 872796 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]([OH:8])=O)[N:3]=[CH:2]1.Cl.CN(C)CCCN=C=NCC.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH2:40][C@@H:41]([CH3:57])[CH2:42][N:43]1[CH:47]=[CH:46][C:45]([C:48]2[CH:55]=[CH:54][C:51]([C:52]#[N:53])=[C:50]([Cl:56])[CH:49]=2)=[N:44]1>CN(C=O)C.O>[Cl:56][C:50]1[CH:49]=[C:48]([C:45]2[CH:46]=[CH:47][N:43]([CH2:42][C@@H:41]([NH:40][C:6]([C:4]3[N:3]=[CH:2][NH:1][CH:5]=3)=[O:8])[CH3:57])[N:44]=2)[CH:55]=[CH:54][C:51]=1[C:52]#[N:53]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67170882(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrileHCID 178524800HCID 178524800, compound

Product 1

HCID 178461751(S)-N-{1-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

4-Imidazolecarboxylic acid (1.00 g, 8.9 mmol) was dissolved in dry DMF (35 ml). Dry 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 2.31 g, 12.0 mmol), HOBt (1.84 g, 12.0 mmol), and DIPEA (4.7 ml, 3.46 g, 26.8 mmol) were added at RT. After stirring for 15 min (S)-4-[1-(2-aminopropyl)-1H-pyrazol-3-yl]-2-chlorobenzonitrile of Example 34© (2.44 g, 9.4 mmol) in dry DMF (15 ml) was added to the solution at RT. Then the solution was stirred for 45 h. Water was added and the product was extracted into ethyl acetate. The organic phase was washed with brine and water, dried and evaporated. The crude product was purified by triturating in hot DCM. The product was filtered and washed with heptane. 1H NMR (400 MHz, DMSO-d6): 1.08 (3H, d), 4.30 (1H, distorted dd), 4.41 (2H, m), 6.95 (1H, d), 7.57 (1H, s), 7.75 (1H, d), 7.85 (1H, d), 8.01 (2H, m), 8.21 (1H, s), 8.30 (1H, d), 12.47 (1H, broad s).

Workup

  1. additionwas added to the solution at RT
  2. extractionthe product was extracted into ethyl acetate
  3. washThe organic phase was washed with brine and water
  4. customdried
  5. customevaporated
  6. customThe crude product was purified
  7. customby triturating in hot DCM
  8. filtrationThe product was filtered
  9. washwashed with heptane

Sources & evidence

ORD record
ord-19bba5d4df6a4421819d240187a6e93c
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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