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Nitrogen → 2-(2-Chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methyl-benzamide

HRID 1472555
Notes
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Reaction equation

HRID 1472555 reaction equation
[CH:1]1(B(O)O)[CH2:3][CH2:2]1.N#N.Br[C:10]1[C:11]([NH:17][C:18]2[CH:27]=[CH:26][CH:25]=[CH:24][C:19]=2[C:20]([NH:22][CH3:23])=[O:21])=[CH:12][C:13]([Cl:16])=[N:14][CH:15]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:16][C:13]1[CH:12]=[C:11]([NH:17][C:18]2[CH:27]=[CH:26][CH:25]=[CH:24][C:19]=2[C:20]([NH:22][CH3:23])=[O:21])[C:10]([CH:1]2[CH2:3][CH2:2]2)=[CH:15][N:14]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 575169042-[(5-Bromo-2-chloro-4-pyridinyl)amino]-N-methylbenzamide

Product 1

HCID 575169032-(2-Chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methyl-benzamideYield 54.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst
HCID 962WaterSolvent
HCID 1140TolueneSolvent

Procedure

A solution of cyclopropylboronic acid (0.38 g, 4.40 mmole, 1.5 eq) in toluene (100 mL) was degassed with N2 at 50° C. for 15 min. To this was added Pd(PPh3)4 (0.17 g, 0.15 mmole, 0.05 eq) and 2-(5-bromo-2-chloro-pyridin-4-ylamino)-N-methyl-benzamide (1 g, 2.93 mmole, 1 eq) and the resulting reaction mixture was again degassed for 30 min. To this a degassed solution K3PO4 (2.49 g, 11.72 mmole, 4 eq) in H2O (4 mL) was added in one portion and the resulting reaction mixture was refluxed for overnight. Solvent was removed under reduced pressure and the residue was diluted with water (100 mL) and then extracted with DCM (3×75 mL). Combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to yield crude product. Crude compound was purified by column chromatography over silica gel (60-120 mesh) using 0.5% MeOH-DCM as the eluant to give the title compound as a pale yellow solid (0.480 g, 54%). 1H-NMR (400 MHz, DMSO-d6): δ 0.60-0.70 (m, 2H), 0.95-1.05 (m, 2H), 1.60-1.71 (m, 1H), 2.76 (d, 3H, J=4.48 Hz), 7.09 (s, 1H), 7.10-7.18 (m, 1H), 7.49-7.60 (m, 2H), 7.68-7.70 (d, 1H, J=7.64 Hz), 7.93 (s, 1H), 8.60-8.70 (m, 1H), 10.22 (s, 1H). LC-MS [M+H]+=302.0.

Workup

  1. customthe resulting reaction mixture
  2. customwas again degassed for 30 min
  3. customthe resulting reaction mixture
  4. temperaturewas refluxed for overnight
  5. customSolvent was removed under reduced pressure
  6. additionthe residue was diluted with water (100 mL)
  7. extractionextracted with DCM (3×75 mL)
  8. dry with materialCombined organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto yield crude product
  12. customCrude compound was purified by column chromatography over silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-6e6733040cf34a18b3cab10149bca266
Source dataset
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09012479B2

Reaction notes

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