Diisopropylethylamine → HCID 117812393, compound

HRID 1481853Notes

Reaction equation

HRID 1481853 reaction equation
[NH2:1][C:2]1[C:3]([N:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH3:35])[CH2:25][CH2:24]2)=[CH:4][C:5]([N:20]([CH3:22])[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:36]1([C:39]2[O:40][CH:41]=[C:42]([C:44](O)=[O:45])[N:43]=2)[CH2:38][CH2:37]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>[CH3:21][N:20]([CH3:22])[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:44]([C:42]2[N:43]=[C:39]([CH:36]3[CH2:38][CH2:37]3)[O:40][CH:41]=2)=[O:45])=[C:3]([N:23]2[CH2:24][CH2:25][N:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH3:35])[CH2:27][CH2:28]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 117812411HCID 117812411, compound

Product 1

HCID 117812393HCID 117812393, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-Amino-2-dimethylamino-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide 7c (111.4 mg, 0.23 mmol, 100 mol %), 2-cyclopropyl-oxazole-4-carboxylic acid 1h (53.5 mg, 0.35 mmol, 150 mol %) and N,N-diisopropylethylamine (0.12 ml, 0.70 mmol, 300 mol %) were combined in N,N-dimethylformamide (2.0 ml) and HATU (132.7 mg, 0.35 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-dimethylamino-5-[3-(2-oxo-pyrrolidin-1-yl)-propylcarbamoyl]-2-(4-o-tolyl-piperazin-1-yl)-phenyl]-amide 7e (100.0 mg; 0.16 mmol, 70.0%) 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-9c5090aa45d04f6dae22aa38d9db2e79
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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