Water → N-(4,5-Difluoro-6-(2-fluoro-4-iodophenylamino)benzo[d]oxazol-7-yl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide

HRID 1914905노트

반응식

HRID 1914905 반응식
C[N+:2]1([O-])[CH2:7][CH2:6][O:5][CH2:4]C1.[F:9][C:10]1C2N=COC=2[C:13]([NH:19][S:20]([C:23]2([CH2:26]C=C)[CH2:25][CH2:24]2)(=[O:22])=[O:21])=[C:12]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([I:36])=[CH:32][C:31]=2[F:37])[C:11]=1[F:38].[OH2:39].[CH2:40]1[CH2:44][O:43]CC1>[Os](=O)(=O)(=O)=O>[F:9][C:10]1[C:7]2[N:2]=[CH:4][O:5][C:6]=2[C:13]([NH:19][S:20]([C:23]2([CH2:26][CH:40]([OH:39])[CH2:44][OH:43])[CH2:25][CH2:24]2)(=[O:21])=[O:22])=[C:12]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([I:36])=[CH:32][C:31]=2[F:37])[C:11]=1[F:38]

참가 물질

6

반응물 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 82029Methyl morpholine oxideHCID 532415631-Allyl-cyclopropanesulfonic acid [4,5-difluoro-6-(2-fluoro-4-iodo-phenylamino)-benzooxazol-7-yl]-amide

생성물 1

HCID 53241564N-(4,5-Difluoro-6-(2-fluoro-4-iodophenylamino)benzo[d]oxazol-7-yl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide수율 17.7%

시약·촉매·용매 1

HCID 30318Osmium Tetroxide촉매

실험 절차

N-Methylmorpholine-N-oxide (34 mg, 0.290 mmol) was added to a solution of 1-allyl-cyclopropanesulfonic acid [4,5-difluoro-6-(2-fluoro-4-iodo-phenylamino)-benzooxazol-7-yl]-amide (1D: 160 mg, 0.290 mmol) in THF (10 mL). This was followed by the addition of osmium tetroxide (7.3 mg, 0.0287 mmol) and water (0.5 mL). The resulting mixture was stirred at room temperature overnight. The reaction mixture was concentrated and diluted with ethyl acetate. The organic layer was washed with water, saturated NaHCO3, brine, dried over anhydrous Na2SO4 and concentrated to afford 150 mg of the crude product. Purification by preparative HPLC, followed by preparative TLC afforded 8 mg of the product (17.7% yield). H1NMR (CDCl3, 300 MHz): δ 8.14 (s, 1H), 7.94 (s, 1H), 7.46-7.36 (m, 1H), 7.3-7.2 (m, 1H), 6.82 (s, 1H), 6.45-6.34 (m, 1H), 4.40-4.26 (m, 2H), 4.20-4.10 (m, 1H), 3.75-3.65 (m, 1H), 3.60-3.50 (m, 1H), 2.62-2.50 (m, 2H), 0.92-0.80 (m, 4H). LCMS: 96.11%, m/z=581.9 (M-1). HPLC: 94.29%.

후처리

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with ethyl acetate
  3. washThe organic layer was washed with water, saturated NaHCO3, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customto afford 150 mg of the crude product
  7. customPurification by preparative HPLC

출처 및 근거

ORD 기록
ord-5d8e2edfcdd544908035b14fb10f7d74
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08614239B2

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