Hydrochloric Acid → 11-(3-Chloro-4-fluorobenzyl)-9-hydroxy-3,4,5,6,12,13-hexahydro-[1,4]oxazocino[3,4-a]-2,6-naphthyridine-1,8,10(11H)-trione

HRID 18030

反応式

HRID 18030 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16](N(C)C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].C[O-:29].[Mg+2].C[O-].Br[CH2:34][CH2:35][CH2:36][CH2:37]Cl.Cl>CO.CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]3[CH2:37][CH2:36][CH2:35][CH2:34][O:17][C:16](=[O:29])[C:12]3=2)[C:7]1=[O:23]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 813641-Bromo-4-chlorobutaneHCID 164537Methanol, magnesium salt (2:1)HCID 178484497HCID 178484497、化合物

生成物 1

HCID 5934472111-(3-Chloro-4-fluorobenzyl)-9-hydroxy-3,4,5,6,12,13-hexahydro-[1,4]oxazocino[3,4-a]-2,6-naphthyridine-1,8,10(11H)-trione

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒2 回HCID 887Methanol溶媒

反応条件

温度
60 °C

実験手順

A mixture of 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide (0.80 g, 2.19 mmol; Example 1, step 9) and magnesium methoxide in methanol (10.6 mL, 6-10% methanol solution available from Aldrich) in DMSO (22 mL) was heated at 60° C. for 30 minutes. Methanol was exhaustively removed under vacuum over 45 minutes. The residual DMSO solution was treated with 1-bromo-4-chlorobutane (1.80 g, 10.50 mmol) and stirred at 60° C. under an atmosphere of nitrogen overnight. The reaction mixture was heated at 100° C. for 3 hrs. The reaction mixture was treated with dilute HCl. The solid precipitated was filtered, dissolved in DMSO, and subjected to reverse phase HPLC purification. Collection and lyophization of appropriate fractions provided the title compound.

後処理

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. temperatureThe reaction mixture was heated at 100° C. for 3 hrs
  3. customThe solid precipitated
  4. filtrationwas filtered
  5. dissolutiondissolved in DMSO
  6. customphase HPLC purification
  7. customCollection and lyophization of appropriate fractions

出典と根拠

ORDレコード
ord-2362b2ad6ef049cf9f91ea51891e3adc
出典データセット
uspto-grants-2010_06
特許番号
US07741315B2

関連ノート

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