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Benzenesulfonamide, 3-amino- → 3-(4-fluoro-2-methoxyphenoxy)-N-(3-sulfamoylphenyl)quinoxaline-2-carboxamide

HRID 2280571
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HRID 2280571 반응식
[F:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:8]([C:17]([OH:19])=O)=[N:9][C:10]3[C:15]([N:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)=[C:4]([O:22][CH3:23])[CH:3]=1.[NH2:24][C:25]1[CH:26]=[C:27]([S:31]([NH2:34])(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C>[F:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:8]([C:17]([NH:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([S:31](=[O:33])(=[O:32])[NH2:34])[CH:26]=3)=[O:19])=[N:9][C:10]3[C:15]([N:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)=[C:4]([O:22][CH3:23])[CH:3]=1
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참가 물질

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반응물 4

HCID 7377Benzenesulfonamide, 3-amino-HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867295573-(4-Fluoro-2-methoxy-phenoxy)quinoxaline-2-carboxylic acid

생성물 1

HCID 783197673-(4-fluoro-2-methoxyphenoxy)-N-(3-sulfamoylphenyl)quinoxaline-2-carboxamide
수율 37.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 3-(4-fluoro-2-methoxy-phenoxy)quinoxaline-2-carboxylic acid (47.1 mg, 0.15 mmol), 3-aminobenzenesulfonamide (31.0 mg, 0.18 mmol), HATU (62.7 mg, 0.16 mmol) and N-methylmorpholine (32.98 μL, 0.30 mmol) in DMF (0.5 mL) was stirred at 50° C. for 30 min. Purification was by reverse phase HPLC using a gradient of 1-99% ACN in Water (HCl modifier). The fractions containing the product were evaporated to dryness. The residue was then taken up in ethyl acetate and water and the pH of the solution was adjusted to −8 with a saturated solution of NaHCO3 in water (˜3 drops). The layers separated and the aqueous layer was extracted with ethyl acetate (3×). All organic were combined, evaporated and purification by silica gel column chromatography using a gradient of ethyl acetate in hexanes (5 to 70%) gave 3-(4-fluoro-2-methoxy-phenoxy)-N-(3-sulfamoylphenyl)quinoxaline-2-carboxamide (2) (26.10 mg, 37%) as a white solid. ESI-MS m/z calc. 468.09, found 469.3 (M+1)+; Retention time: 1.49 minutes (3 minutes run). 1H NMR (400 MHz, DMSO) δ 11.27 (s, 1H), 8.42 (s, 1H), 8.18 (d, J=8.0 Hz, 1H), 7.97-7.87 (m, 1H), 7.86-7.71 (m, 3H), 7.68-7.56 (m, 2H), 7.44 (s, 2H), 7.34 (dd, J=8.7, 5.9 Hz, 1H), 7.16 (dd, J=10.8, 2.9 Hz, 1H), 6.88 (ddd, J=8.6, 2.9 Hz, 1H), 3.71 (s, 3H) ppm.

후처리

  1. customPurification
  2. additionThe fractions containing the product
  3. customwere evaporated to dryness
  4. customThe layers separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×)
  6. customevaporated
  7. custompurification by silica gel column chromatography

출처 및 근거

ORD 기록
ord-40d27c1fe7df4f35818269b8250987ca
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09139529B2

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