1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-5-acetyl-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-3-carboxamide

HRID 872474Notes

Reaction equation

HRID 872474 reaction equation
[C:1]([C:4]1[CH:8]=[C:7]([C:9]([OH:11])=O)[NH:6][N:5]=1)(=[O:3])[CH3:2].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[NH2:42][C@@H:43]([CH3:59])[CH2:44][N:45]1[CH:49]=[CH:48][C:47]([C:50]2[CH:57]=[CH:56][C:53]([C:54]#[N:55])=[C:52]([Cl:58])[CH:51]=2)=[N:46]1>C(Cl)Cl>[C:1]([C:4]1[CH:8]=[C:7]([C:9]([NH:42][C@@H:43]([CH3:59])[CH2:44][N:45]2[CH:49]=[CH:48][C:47]([C:50]3[CH:57]=[CH:56][C:53]([C:54]#[N:55])=[C:52]([Cl:58])[CH:51]=3)=[N:46]2)=[O:11])[NH:6][N:5]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 167673463-acetyl-1H-pyrazole-5-carboxylic acidHCID 67170882(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile

Product 1

HCID 52919826(S)-5-acetyl-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-3-carboxamideYield 32.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

3-Acetyl-1H-pyrazole-5-carboxylic acid (0.59 g; 3.84 mmol) and DIPEA (1.0 ml; 5.75 mmol) were dissolved in 4 ml of dry DCM. Anhydrous HOBt (0.78 g; 5.75 mmol) and EDCI (1.10 g; 5.75 mmol) were added at RT. (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (1.00 g; 3.84 mmol) was dissolved in 4 ml of DCM and the reaction was stirred for overnight at RT. 40 ml of DCM was added and organic layer washed with 3×15 ml of water. Combined water phases were washed with 2×20 ml of DCM. Both organic phases were dried over Na2SO4, filtered and evaporated to dryness. Both crude product fractions were combined and purified by CombiFlash (2% MeOH in DCM). Product fractions were combined and evaporated to give 497 mg of product. 1H-NMR (400 MHz; d6-DMSO): δ 1.16 (d, 3H, J=6.7 Hz), 2.49 (s, 3H), 4.31 (m, 2H), 4.46 (sept, 1H, J=6.7 Hz), 6.93 (d, 1H, J=2.4 Hz), 7.31 (s, 1H), 7.81 (d, 1H, J=2.4 Hz), 7.92 (d, 1H, J=7.9 Hz), 7.97 (d, 1H, J=8.1 Hz), 8.03 (d, 1H, J=1.3 Hz), 8.48 (d, 1H, J=8.5 Hz), 14.16 (s, 1H).

Workup

  1. washorganic layer washed with 3×15 ml of water
  2. washCombined water phases were washed with 2×20 ml of DCM
  3. dry with materialBoth organic phases were dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. custompurified by CombiFlash (2% MeOH in DCM)
  7. customevaporated

Sources & evidence

ORD record
ord-d1718a823f06492e97b505424421f02a
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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