Diisopropylethylamine → 2,6-dichloro-N-(2-((1R,2R)-2-chlorocyclopropanecarboxamido)pyridin-4-yl)benzamide

HRID 449908ノート

反応式

HRID 449908 の反応式
[NH2:1][C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:18])[C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:4][N:3]=1.[Cl:19][CH:20]1[CH2:22][CH:21]1[C:23](O)=[O:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:16][C:15]1[CH:14]=[CH:13][CH:12]=[C:11]([Cl:17])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:23]([C@H:21]2[CH2:22][C@H:20]2[Cl:19])=[O:24])[CH:7]=1)=[O:18]

参加物

7

反応物 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 133995232-Chlorocyclopropane-1-carboxylic acidHCID 59618313N-(2-aminopyridin-4-yl)-2,6-dichlorobenzamide

生成物 1

HCID 596180252,6-dichloro-N-(2-((1R,2R)-2-chlorocyclopropanecarboxamido)pyridin-4-yl)benzamide収率 12%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
110 °C

実験手順

To a solution of N-(2-aminopyridin-4-yl)-2,6-dichlorobenzamide (150 mg, 0.54 mmol), 2-chlorocyclopropanecarboxylic acid (66 mg, 0.54 mmol) and HATU (381 mg, 1.08 mmol) in dry DMF (4.5 mL) was added DIPEA (144 mg, 1.08 mmol). The mixture was stirred at 110° C. in a microwave reactor for 1 hour. The mixture was cooled to room temperature and diluted with EtOAc (30 mL). The organic solution was washed with water (10 mL) and brine (10 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to give the desired compounds.

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. washThe organic solution was washed with water (10 mL) and brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

出典と根拠

ORDレコード
ord-0b50e7736efd4c7bac27045464ccb921
出典データセット
uspto-grants-2013_07
特許番号
US08486950B2

反応ノート

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