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

HRID 1472559ノート

反応式

HRID 1472559 の反応式
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

参加物

9

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-ec67b7357802415da7c9131889d82a49
出典データセット
uspto-grants-2015_04
特許番号
US09012479B2

反応ノート

読み込み中…