Hydrochloric Acid → HCID 89657375、化合物

HRID 930925ノート

反応式

HRID 930925 の反応式
[F:1][C:2]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][C:6]=1[C:15]1[C:16]2[CH:25]=[C:24](C(OCC)=O)[NH:23][C:17]=2[C:18](=[O:22])[N:19]([CH3:21])[CH:20]=1.C[Mg]Br.Cl.O1C[CH2:43][CH2:42][CH2:41]1>>[F:1][C:2]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][C:6]=1[C:15]1[C:16]2[CH:25]=[C:24]([C:42]([CH3:43])=[CH2:41])[NH:23][C:17]=2[C:18](=[O:22])[N:19]([CH3:21])[CH:20]=1

参加物

5

反応物 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 89657495HCID 89657495、化合物HCID 178418573HCID 178418573、化合物

生成物 1

HCID 89657375HCID 89657375、化合物収率 25%

反応条件

温度
0 °C

実験手順

To a solution of Example 252f (0.10 g, 0.20 mmol) in tetrahydrofuran (6 mL) stirring at 0° C. was added methylmagnesium bromide (0.498 mL, 0.498 mmol). The reaction mixture was stirred at 0° C. for 1 hour, and then aqueous HCl (1 M, 2 mL) was added. The reaction mixture was concentrated and partitioned between saturated aqueous sodium chloride (10 mL) and ethyl acetate. The organic phase was washed with saturated aqueous sodium chloride (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by reverse phase-HPLC (C 18 40-90% gradient acetonitrile:water (0.1% TFA)) to provide the title compound (25 mg, 25% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.05 (s, 1H), 7.98 (d, J=2.4 Hz, 1H), 7.87 (dd, J=8.7, 2.4 Hz, 1H), 7.61-7.36 (m, 3H), 7.18 (t, J=8.6 Hz, 1H), 6.98 (d, J=8.3 Hz, 1H), 6.34 (d, J=2.2 Hz, 1H), 5.85 (s, 1H), 5.07 (s, 1H), 3.60 (s, 3H), 3.26 (s, 3H), 2.02 (s, 3H). MS (ESI+) m/z 471.1 (M+1)+.

後処理

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between saturated aqueous sodium chloride (10 mL) and ethyl acetate
  3. washThe organic phase was washed with saturated aqueous sodium chloride (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase-HPLC (C 18 40-90% gradient acetonitrile:water (0.1% TFA))

出典と根拠

ORDレコード
ord-bd86653c48ec4ba5a6d515736676f9a8
出典データセット
uspto-grants-2016_03
特許番号
US09296741B2

反応ノート

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