Acetonitrile → 3,5-Dichloro-4-[4-(6-fluoromethyl-pyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-benzonitrile

HRID 626691ノート

反応式

HRID 626691 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:28])[C:9]=1[N:10]1[CH:27]=[C:13]2[C:14]([NH:18][C:19]3[CH:24]=[C:23]([CH2:25][OH:26])[N:22]=[CH:21][N:20]=3)=[N:15][CH:16]=[CH:17][C:12]2=[N:11]1)[C:5]#[N:6].CCN(S(F)(F)[F:35])CC.C(#N)C>C(Cl)Cl.O>[OH-:26].[NH4+:6].[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:28])[C:9]=1[N:10]1[CH:27]=[C:13]2[C:14]([NH:18][C:19]3[CH:24]=[C:23]([CH2:25][F:35])[N:22]=[CH:21][N:20]=3)=[N:15][CH:16]=[CH:17][C:12]2=[N:11]1)[C:5]#[N:6]

参加物

7

反応物 3

HCID 6342AcetonitrileHCID 123472(Diethylamino)sulfur trifluorideHCID 696713413,5-Dichloro-4-[4-(6-hydroxymethyl-pyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-benzonitrile

生成物 2

HCID 14923Ammonium Hydroxide収率 0.1%HCID 677022303,5-Dichloro-4-[4-(6-fluoromethyl-pyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-benzonitrile収率 28.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

To a suspension of 3,5-dichloro-4-[4-(6-hydroxymethyl-pyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-benzonitrile (70 mg, 0.17 mmol) in DCM (5 mL) at −25° C. was added DAST (34 μL, 0.25 mmol). The reaction mixture was warmed to room temperature over 1 hour. The reaction mixture was partitioned between DCM and sodium bicarbonate (sat. aq.). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate in cyclohexane) then by HPLC (5 to 98% acetonitrile in water with 0.1% ammonium hydroxide) to afford the title compound as a white solid (10 mg, 14% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.96 (s, 1H), 9.23 (s, 1H), 8.81 (s, 1H), 8.69 (s, 1H), 8.49 (s, 2H), 8.02 (d, J=6.4 Hz, 1H), 7.27 (d, J=6.4 Hz, 1H), 5.50 (d, J=46.3 Hz, 2H). LCMS (Method B): RT=2.96 min, m/z: 414 [M+H+].

後処理

  1. customThe reaction mixture was partitioned between DCM and sodium bicarbonate (sat. aq.)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate in cyclohexane)

出典と根拠

ORDレコード
ord-dae28d60c03447f8ac8701b0937e4a15
出典データセット
uspto-grants-2016_04
特許番号
US09309240B2

反応ノート

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