Sodium Iodide → Methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

HRID 2205405노트

반응식

HRID 2205405 반응식
CO[C:3](=[O:19])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:6][C:5]=1[CH2:17]Cl.[CH3:20][O:21][C:22](=[O:35])[CH2:23][NH:24]S(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].C[O-].[Na+]>CN(C=O)C.CO.O.C(O)(=O)C>[CH3:20][O:21][C:22]([C:23]1[N:24]=[CH:17][C:5]2[C:4]([C:3]=1[OH:19])=[CH:9][CH:8]=[C:7]([O:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH:6]=2)=[O:35]

참가 물질

10

반응물 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 562880Methyl 2-(4-methylphenylsulfonamido)acetateHCID 10942334Sodium MethoxideHCID 86709143Methyl 2-(chloromethyl)-4-phenoxybenzoate

생성물 1

HCID 86709142Methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

시약·촉매·용매 4

HCID 176Acetic Acid용매HCID 887Methanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A reactor was charged with a solution of 2-chloromethyl-4-phenoxybenzoic acid methyl ester (˜68 Kg) in DMF, and stirring was initiated. The reactor was then charged with p-toluenesulfonylglycine methyl ester (66 Kg), potassium carbonate (60 Kg), and sodium iodide (4 Kg). The mixture was heated to at least 50° C. until reaction completion. The mixture was cooled. Sodium methoxide in methanol was charged and the mixture was stirred until reaction completion. Acetic acid and water were added, and the mixture was stirred, filtered and washed with water. Solid was purified by acetone trituration and dried in an oven giving 1a (Yield from step b): 58%; HPLC: 99.4%). 1H NMR (200 MHz, DMSO-d6) δ 11.60 (s, 1 H), 8.74 (s, 1H), 8.32 (d, J=9.0 Hz, 1 H), 7.60 (dd, J=2.3 & 9.0 Hz, 1H), 7.49 (m, 3 H), 7.24 (m, 3 H), 3.96 (s, 3 H); MS-(+)-ion M+1=296.09

후처리

  1. temperatureThe mixture was heated to at least 50° C. until reaction completion
  2. temperatureThe mixture was cooled
  3. stirringthe mixture was stirred until reaction completion
  4. stirringthe mixture was stirred
  5. filtrationfiltered
  6. washwashed with water
  7. customSolid was purified by acetone trituration
  8. customdried in an oven

출처 및 근거

ORD 기록
ord-8b3f89d16d7e4e5b94cb068c972aceac
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09371288B2

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