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

HRID 62513Notes

Reaction equation

HRID 62513 reaction equation
N#N.Br[C:4]1[C:5]([NH:11][C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2[C:14]([NH:16][O:17][CH3:18])=[O:15])=[CH:6][C:7]([Cl:10])=[N:8][CH:9]=1.[CH:23]1(B(O)O)[CH2:25][CH2:24]1.[Na+].[Br-].[F-].[K+]>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.C1(C)C=CC=CC=1>[Cl:10][C:7]1[CH:6]=[C:5]([NH:11][C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2[C:14]([NH:16][O:17][CH3:18])=[O:15])[C:4]([CH:23]2[CH2:25][CH2:24]2)=[CH:9][N:8]=1

Participants

9

Reactant 5

HCID 947NitrogenHCID 253881Sodium BromideHCID 522689Potassium FluorideHCID 2760897Cyclopropylboronic acidHCID 575169052-[(5-bromo-2-chloro-4-pyridinyl)amino]-N-methoxyBenzamide

Product 1

HCID 575169062-(2-Chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methoxy-benzamideYield 53%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

In a sealable tube toluene (50 mL) was degassed with N2 at 50° C. for 15 min and to this 2-(5-bromo-2-chloro-pyridin-4-ylamino)-N-methoxy-benzamide (1.5 g, 4.21 mmole, 1 eq), cyclopropylboronic acid (1.4 g, 16.85 mmole, 4 eq) and Pd(PPh3)4 (0.24 g, 0.21 mmole, 0.05 eq) were added and resulting mixture was degassed for 30 min. To this NaBr (0.44 g, 4.33 mmole, 1.03 eq) and a solution of KF (0.8 g, 13.90 mmole, 3.3 eq) in H2O (3 mL) were added; again degassed with N2 for 15 min. The tube was sealed and the resulting mixture was heated at 100° C. for 24 h. After completion of reaction, reaction mixture was allowed to cool at room temperature, poured into water (100 mL) and extracted with toluene (2×50 mL). Combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude compound was purified by washing with 0.5% DCM-Et2O to give titled compound as pale yellow solid (0.7 g, 53%). 1H-NMR (400 MHz, DMSO-d6): δ 0.57-072 (m, 2H), 0.97-1.10 (m, 2H), 1.62-1.75 (m, 1H), 3.68 (s, 3H), 7.02 (s, 1H), 7.11-7.20 (m, 1H), 7.51-7.67 (m, 3H), 7.94 (s, 1H), 9.62 (s, 1H), 11.92 (brs, 1H). LC-MS [M+H]+=318.2.

Workup

  1. additionwere added
  2. customresulting mixture
  3. customwas degassed for 30 min
  4. customagain degassed with N2 for 15 min
  5. customThe tube was sealed
  6. customAfter completion of reaction, reaction mixture
  7. temperatureto cool at room temperature
  8. extractionextracted with toluene (2×50 mL)
  9. dry with materialCombined organic layer was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe crude compound was purified
  13. washby washing with 0.5% DCM-Et2O

Sources & evidence

ORD record
ord-6f1cd5ff86f74161b75a638967f9a947
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Reaction notes

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