Diisopropylethylamine → HCID 117812394, compound

HRID 1481856Notes

Reaction equation

HRID 1481856 reaction equation
[NH2:1][C:2]1[C:3]([N:25]2[CH2:30][CH2:29][N:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[CH3:37])[CH2:27][CH2:26]2)=[CH:4][C:5]([O:20][CH2:21][CH2:22][O:23][CH3:24])=[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:38]1([C:41]2[O:42][CH:43]=[C:44]([C:46](O)=[O:47])[N:45]=2)[CH2:40][CH2:39]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>[CH3:24][O:23][CH2:22][CH2:21][O: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:46]([C:44]2[N:45]=[C:41]([CH:38]3[CH2:40][CH2:39]3)[O:42][CH:43]=2)=[O:47])=[C:3]([N:25]2[CH2:26][CH2:27][N:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[CH3:37])[CH2:29][CH2:30]2)[CH:4]=1

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 131736658HCID 131736658, compound

Product 1

HCID 117812394HCID 117812394, compoundYield 77.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-Amino-2-(2-methoxy-ethoxy)-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide 8d (91.7 mg, 0.18 mmol, 100 mol %), 2-cyclopropyl-oxazole-4-carboxylic acid 1h (41.3 mg, 0.27 mmol, 150 mol %) and N,N-diisopropylethylamine (0.09 ml; 0.54 mmol; 300 mol %) were combined in N,N-dimethylformamide (4.0 ml) and HATU (102.6 mg, 0.27 mmol, 150 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 reverse phase HPLC (methanol+0.1% formic acid/water) to afford 2-cyclopropyl-oxazole-4-carboxylic acid [4-(2-methoxy-ethoxy)-5-[3-(2-oxo-pyrrolidin-1-yl)-propylcarbamoyl]-2-(4-o-tolyl-piperazin-1-yl)-phenyl]-amide 8f (89.3 mg; 0.14 mmol, 77%) 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 reverse phase HPLC (methanol+0.1% formic acid/water)

Sources & evidence

ORD record
ord-016709397c13445796aafe26dece6a92
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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