1,2-Dichloroethane → HCID 46215629、化合物

HRID 62543

反応式

HRID 62543 の反応式
[Cl:1][C:2]1[C:3]([NH:18][C:19]2[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:20]=2[C:21](O)=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:16])[CH3:15])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1.C1C=CC2[N:37]([OH:38])N=NC=2C=1.[CH2:39](Cl)CCl.CCN(C(C)C)C(C)C>CN(C)C=O.C(O)(=O)C.O>[Cl:1][C:2]1[C:3]([NH:18][C:19]2[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:20]=2[C:21]([NH:37][O:38][CH3:39])=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:15])[CH3:16])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1

参加物

8

反応物 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 667695202-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzoic acid

生成物 1

HCID 46215629HCID 46215629、化合物収率 30.5%

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzoic acid (3.2 g, 7.92 mmol) in N,N-dimethylformamide (DMF) (50 mL) was added HOBT (1.456 g, 9.51 mmol) and EDC (1.823 g, 9.51 mmol) and the reaction mixture was stirred for 30 min. To this solution was added O-methoxylamine hydrochloride (0.794 g, 9.51 mmol). After 30 min the reaction mixture was cooled to 0° C. and DIEA (4.14 mL, 23.77 mmol) was added. The reaction mixture was stirred at the room temperature 24 hr. Water (100 mL) was added followed by acetic acid (1 mL) and the solution was extracted with 2×50 ml of ethyl acetate. The combined organic layers were washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and evaporated. The oil was suspended in dichloromethane and filtered. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluoro-N-(methyloxy)benzamide (1.1 g, 2.414 mmol, 30.5% yield) was isolated as a white solid; 1H NMR (400 MHz, DMSO-d6) ppm 1.24 (d, J=6.57 Hz, 6 H) 2.08 (s, 3 H) 3.68 (s, 3 H) 4.33 (quin, J=6.57 Hz, 1 H) 5.83 (d, J=5.05 Hz, 1 H) 5.84 (s, 1 H) 7.30-7.49 (m, 2 H) 7.49-7.63 (m, 1 H) 7.92 (s, 1 H) 8.41 (d, J=4.29 Hz, 2 H) 11.85 (s, 1 H); HPLC Rt=2.18 min, MS (ESI): 433.3 [M+H]+.

後処理

  1. stirringThe reaction mixture was stirred at the room temperature 24 hr
  2. extractionthe solution was extracted with 2×50 ml of ethyl acetate
  3. washThe combined organic layers were washed with 2×50 ml
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. filtrationfiltered

出典と根拠

ORDレコード
ord-1328123b07264bc4a2f138af4dc2d07f
出典データセット
uspto-grants-2016_09
特許番号
US09446034B2

関連ノート

読み込み中…