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

HRID 1914905ノート

反応式

HRID 1914905 の反応式
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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 30318Osmium Tetroxide触媒

実験手順

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%.

後処理

  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

出典と根拠

ORDレコード
ord-5d8e2edfcdd544908035b14fb10f7d74
出典データセット
uspto-grants-2013_12
特許番号
US08614239B2

反応ノート

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