1,2-Dichloroethane → HCID 67494878, compound

HRID 1776028Notes

Reaction equation

HRID 1776028 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20](O)=[O:21])=[CH:16][N:15]=2)[C@H:10]([CH3:23])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CC(N(C)C)=O.[Br:44][C:45]1[CH:51]=[CH:50][C:48]([NH2:49])=[CH:47][C:46]=1[F:52].C(N(CC)C(C)C)(C)C>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:21])[NH:49][C:48]3[CH:50]=[CH:51][C:45]([Br:44])=[C:46]([F:52])[CH:47]=3)=[CH:16][N:15]=2)[C@H:10]([CH3:23])[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 31374DimethylacetamideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 8218484-Bromo-3-fluoroanilineHCID 67495464HCID 67495464, compound

Product 1

HCID 67494878HCID 67494878, compoundYield 43.1%

Procedure

A solution of (R)-4-(5-carboxy-pyridin-2-yl)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (150 mg, 0.47 mmol, Preparation 33), EDC (130 mg, 0.70 mmol), and HOAt (95 mg, 0.70 mmol) dissolved in DMA (4.3 mL, 47 mmol) was stirred at RT for 30 min and then 4-bromo-3-fluoroaniline (89 mg, 0.47 mmol) was added, followed by N,N-diisopropylethylamine (0.2 mL, 1.2 mmol). The reaction mixture was stirred at RT overnight and extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate, filtered, concentrated, and purified by silica gel chromatography (eluted: 0-40% EtOAc:hexanes) to provide the title compound as a light yellow oil (100 mg, 40% yield). (m/z): [M+H]+ calcd for C22H26BrFN4O3 493.12 found 493.2.

Workup

  1. stirringThe reaction mixture was stirred at RT overnight
  2. extractionextracted with ethyl acetate/water
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (eluted: 0-40% EtOAc:hexanes)

Sources & evidence

ORD record
ord-cedc8a3c9892462c8ab8d2d30f39c768
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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