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

반응식

HRID 18030 반응식
[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]

참가 물질

7

반응물 4

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

생성물 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

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매2회HCID 887Methanol용매

반응 조건

온도
60 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-2362b2ad6ef049cf9f91ea51891e3adc
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741315B2

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