Diisopropylethylamine → HCID 89692821, compound

HRID 1481851Notes

Reaction equation

HRID 1481851 reaction equation
[NH2:1][C:2]1[C:3]([N:22]2[CH2:27][CH2:26][N:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[CH3:34])[CH2:24][CH2:23]2)=[CH:4][C:5]([CH2:20][CH3:21])=[C:6]([CH:19]=1)[C:7]([NH:9][CH2:10][CH2:11][CH2:12][N:13]1[CH2:17][CH2:16][CH2:15][C:14]1=[O:18])=[O:8].[CH:35]1([C:38]2[O:39][CH:40]=[C:41]([C:43](O)=[O:44])[N:42]=2)[CH2:37][CH2:36]1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.O>[CH2:20]([C:5]1[C:6]([C:7](=[O:8])[NH:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])=[CH:19][C:2]([NH:1][C:43]([C:41]2[N:42]=[C:38]([CH:35]3[CH2:37][CH2:36]3)[O:39][CH:40]=2)=[O:44])=[C:3]([N:22]2[CH2:23][CH2:24][N:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[CH3:34])[CH2:26][CH2:27]2)[CH:4]=1)[CH3:21]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 252192732-Cyclopropyl-1,3-oxazole-4-carboxylic acidHCID 89690509HCID 89690509, compound

Product 1

HCID 89692821HCID 89692821, compoundYield 50.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-Amino-2-ethyl-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide 6b (36.0 mg, 0.08 mmol, 100 mol %), 2-cyclopropyl-oxazole-4-carboxylic acid 1 h (17.8 mg, 0.12 mmol, 150 mol %) and N,N-diisopropylethylamine (0.04 ml, 0.23 mmol, 300 mol %) were combined in N,N-dimethylformamide (2.0 ml) and HATU (44.3 mg, 0.12 mmol, mol %) was added and the reaction was stirred at room temperature for 16 h. The reaction was then diluted with water and extracted three times with ethyl acetate. The combined organics were dried over sodium sulfate and then concentrated to a residue that was purified by column chromatography (dichloromethane to 10% methanol/dichloromethane) to afford 2-cyclopropyl-oxazole-4-carboxylic acid [4-ethyl-5-[3-(2-oxo-pyrrolidin-1-yl)-propylcarbamoyl]-2-(4-o-tolyl-piperazin-1-yl)-phenyl]-amide 6c (23.4 mg; 0.04 mmol, 50.3%) as a white solid.

Workup

  1. extractionextracted three times with ethyl acetate
  2. dry with materialThe combined organics were dried over sodium sulfate
  3. concentrationconcentrated to a residue that
  4. customwas purified by column chromatography (dichloromethane to 10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-5b6041b6c62942e88838134360e90462
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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