Hydrochloric Acid → Azd-8330

HRID 2068925ノート

反応式

HRID 2068925 の反応式
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:15]=[C:14]([CH3:16])[C:13](=[O:17])[N:12]([CH3:18])[C:11]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=1[F:27])=[O:9])=C.Cl>C(OCC)(=O)C>[F:27][C:21]1[CH:22]=[C:23]([I:26])[CH:24]=[CH:25][C:20]=1[NH:19][C:11]1[N:12]([CH3:18])[C:13](=[O:17])[C:14]([CH3:16])=[CH:15][C:10]=1[C:8]([NH:7][O:6][CH2:5][CH2:4][OH:3])=[O:9]

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 574691682-(2-fluoro-4-iodophenylamino)-1,5-dimethyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridine-3-carboxamide

生成物 1

HCID 16666708Azd-8330

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

To a rapidly stirred mixture of 2-(2-fluoro-4-iodophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-vinyloxyethoxy)-amide (4.2 g, 8.52 mmol) (prepared according to Example 16A, Step 2) above in ethyl acetate (126.00 mL) was added hydrogen chloride (17.05 mL, 17.0493 g, 17.05 mmol). After 2 hours, less than 1% of the starting material remained (by HPLC analysis) and the phases were allowed to settle. The lower aqueous phase was separated and discarded and the organic phase was washed with sodium chloride (42 mL, 15% wt/vol, then 2×25 mL, 9% wt/vol). The volume was then reduced by distillation of solvent (44 mL) at atmospheric pressure (65° C. head temperature). The solution was then cooled to 70° C., and Form 1, 2-(2-fluoro-4-iodophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide (40.3265 mg), made according to Example 16A, Step 4, was added. The mixture was stirred for 20 hours at 70° C. The temperature was reduced to 24° C. over 4 hours 15 minutes, and then lowered to 1° C. for 1 hour. The slurry was then filtered, the cake was washed with cold ethyl acetate (17 mL) and the solid was dried in a vacuum oven at 45° C., to provide 2-(2-fluoro-4-iodophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide Form 1 (3.15 g, 76%).

後処理

  1. customThe lower aqueous phase was separated
  2. washthe organic phase was washed with sodium chloride (42 mL, 15% wt/vol, then 2×25 mL, 9%
  3. distillationThe volume was then reduced by distillation of solvent (44 mL) at atmospheric pressure (65° C. head temperature)
  4. additionwas added
  5. waitThe temperature was reduced to 24° C. over 4 hours 15 minutes
  6. waitlowered to 1° C. for 1 hour
  7. filtrationThe slurry was then filtered
  8. washthe cake was washed with cold ethyl acetate (17 mL)
  9. customthe solid was dried in a vacuum oven at 45° C.

出典と根拠

ORDレコード
ord-d79c2b9b9fe8413ab45edd27740c04f0
出典データセット
uspto-grants-2012_10
特許番号
US08299076B2

反応ノート

読み込み中…