Diisopropylethylamine → HCID 178461748, compound

HRID 872821Notes

Reaction equation

HRID 872821 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=O)=[N:2]1.CCN(C(C)C)C(C)C.[NH2:18][C@@H:19]([CH3:35])[CH2:20][N:21]1[CH:25]=[CH:24][C:23]([C:26]2[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[C:28]([Cl:34])[CH:27]=2)=[N:22]1>C(Cl)Cl>[Cl:34][C:28]1[CH:27]=[C:26]([C:23]2[CH:24]=[CH:25][N:21]([CH2:20][C@@H:19]([NH:18][C:6]([C:3]3[CH:4]=[CH:5][NH:1][N:2]=3)=[O:8])[CH3:35])[N:22]=2)[CH:33]=[CH:32][C:29]=1[C:30]#[N:31]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 67170882(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrileHCID 178524567HCID 178524567, compound

Product 1

HCID 178461748HCID 178461748, compoundYield 36.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1H-pyrazole-3-carboxylic acid (89 mg, 0.767 mmol) in DCM (5 ml), was added DIPEA (0.40 ml, 2.30 mmol). O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniutnhexafluorophosphate (HBTU, 291.0 mg, 0.767 mmol) at RT. The mixture was stirred for 15 min and solid (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (200 mg, 0.767 mmol) was added. The reaction was stirred overnight at RT. The solvent was evaporated and water was added. The pH of the water phase was adjusted to 9-10 and the product was extracted to DCM. The organic layer was washed with water and brine, dried over Na2SO4 and evaporated. The crude product was purified with flash chromatography (DCM/EtOAc gradient) to give title compound 100 mg. 1H-NMR (400 MHz; d6-DMSO): δ 1.11 (d, 3H), 4.36 (m, 3H), 6.58 (t, 1H), 6.93 (d, 1H), 7.79 (m, 1H), 7.82 (d, 1H), 7.98 (d, 2H), 8.08 (bs, 1H), 8.25 (d, 1H), 13.20 (s, 1H).

Workup

  1. customat RT
  2. stirringThe reaction was stirred overnight at RT
  3. customThe solvent was evaporated
  4. additionwater was added
  5. extractionthe product was extracted to DCM
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. customThe crude product was purified with flash chromatography (DCM/EtOAc gradient)

Sources & evidence

ORD record
ord-43b647a23d364e8793df9bd7b9ee8ffa
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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