Diisopropylethylamine → N-(3-Bromo-2-methylphenyl)-3-chloro-2-pyridineacetamide

HRID 523260Notes

Reaction equation

HRID 523260 reaction equation
[Cl:1][C:2]1[C:3]([CH2:8][C:9]([O-:11])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.[Na+].[Br:13][C:14]1[C:15]([CH3:21])=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].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.CCOC(C)=O>[Br:13][C:14]1[C:15]([CH3:21])=[C:16]([NH:17][C:9](=[O:11])[CH2:8][C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1235383-Bromo-o-toluidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 91667886HCID 91667886, compound

Product 1

HCID 117760690N-(3-Bromo-2-methylphenyl)-3-chloro-2-pyridineacetamideYield 89%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of sodium 2-(3-chloropyridin-2-yl)acetate (7.39 g, 38 mmol), 3-bromo-2-methylaniline (4.7 mL, 38.4 mmol), DIEA (13.3 mL, 76 mmol) and HATU (14.6 g, 38.4 mmol) in DMF (127 mL) was stirred at room temperature. After 90 min the mixture was diluted with EtOAc and washed twice with 10% LiCl, then with brine. The combined aqueous layers were extracted with EtOAc, and the combined organic phases were dried and concentrated to a small volume. The solution was seeded with a crystal from an earlier batch and allowed to stand overnight to provide a precipitate which was collected by filtration and washed with 50% EtOAc-hexanes to provide a white solid. The filtrate was concentrated and recrystallized similarly three times to provide additional solid. The solids were combined to give N-(3-bromo-2-methylphenyl)-2-(3-chloropyridin-2-yl)acetamide as a white solid (11.43 g, 89% yield). Mass spectrum m/z 339, 341 (M+H)+. 1H NMR (400 MHz, chloroform-d) δ 9.76 (br. s., 1H), 8.52 (d, J=3.5 Hz, 1H), 7.92 (d, J=7.9 Hz, 1H), 7.80 (dd, J=8.1, 1.1 Hz, 1H), 7.36 (d, J=7.9 Hz, 1H), 7.32-7.23 (m, 1H), 7.06 (t, J=8.0 Hz, 1H), 4.16 (s, 2H), 2.39 (s, 3H).

Workup

  1. washwashed twice with 10% LiCl
  2. extractionThe combined aqueous layers were extracted with EtOAc
  3. customthe combined organic phases were dried
  4. concentrationconcentrated to a small volume
  5. customto provide a precipitate which
  6. filtrationwas collected by filtration
  7. washwashed with 50% EtOAc-hexanes
  8. customto provide a white solid
  9. concentrationThe filtrate was concentrated
  10. customrecrystallized similarly three times
  11. customto provide additional solid

Sources & evidence

ORD record
ord-4f43ffe0d3144e88b774c0b84d3270af
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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