Diisopropylethylamine → (2S,4S)-2-(2-Amino-6-bromo-naphthalen-1-ylcarbamoyl)-4-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1500526Notes

Reaction equation

HRID 1500526 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH2:13])[C:8]=2[NH2:12])[CH:3]=1.[C:14]([O:18][C:19]([N:21]1[CH2:25][C@@H:24]([CH3:26])[CH2:23][C@H:22]1[C:27](O)=[O:28])=[O:20])([CH3:17])([CH3:16])[CH3:15].CCN(C(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=O)C>[C:14]([O:18][C:19]([N:21]1[CH2:25][C@@H:24]([CH3:26])[CH2:23][C@H:22]1[C:27](=[O:28])[NH:12][C:8]1[C:9]2[C:4](=[CH:3][C:2]([Br:1])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[NH2:13])=[O:20])([CH3:16])([CH3:17])[CH3:15]

Participants

6

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 220970716-Bromonaphthalene-1,2-diamineHCID 26596883(4S)-1-(tert-Butoxycarbonyl)-4-methyl-L-proline

Product 1

HCID 86700516(2S,4S)-2-(2-Amino-6-bromo-naphthalen-1-ylcarbamoyl)-4-methyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-bromo-naphthalene-1,2-diamine (2.0 g, 8.5 mmol) in DMF (150 mL) was added (2S,4S)-4-methyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (2.14 g, 10.2 mmol), DIPEA (3.29 g, 25.5 mmol), and HATU (4.84 g, 12.7 mmol). The reaction mixture was stirred at RT overnight and extracted with EtOAc/H2O (150 mL). The organic layer was dried over Na2SO4, filtered, concentrated, and purified by silica gel chromatography (2:1 EtOAc:petroleum ether) to provide the title intermediate (1.6 g)

Workup

  1. extractionextracted with EtOAc/H2O (150 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by silica gel chromatography (2:1 EtOAc:petroleum ether)

Sources & evidence

ORD record
ord-dddfd7de4c4c43d59d8c3cfea95c6506
Source dataset
uspto-grants-2015_12
Patent number
US09206159B2

Reaction notes

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