Hydrochloric Acid → N-(5-{[4-(1H-Indol-3-yl)pyrimidin-2-yl]amino}-4-methoxy-2-{4-methylpiperazin-1-yl}phenyl)prop-2-enamide

HRID 1842625ノート

反応式

HRID 1842625 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17]3[CH:18]=[C:19]([NH2:32])[C:20]([N:25]4[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]4)=[CH:21][C:22]=3[O:23][CH3:24])[N:11]=2)=[CH:2]1.CCN(C(C)C)C(C)C.[C:42](Cl)(=[O:45])[CH:43]=[CH2:44].Cl>C(Cl)Cl.CO.C(Cl)Cl.CC1CCCO1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17]3[C:22]([O:23][CH3:24])=[CH:21][C:20]([N:25]4[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]4)=[C:19]([NH:32][C:42](=[O:45])[CH:43]=[CH2:44])[CH:18]=3)[N:11]=2)=[CH:2]1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 13140Acryloyl chlorideHCID 81531Diisopropylethylamine2 回HCID 86677249N'-[4-(1H-indol-3-yl)pyrimidin-2-yl]-4-methoxy-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine2 回

生成物 1

HCID 73292545N-(5-{[4-(1H-Indol-3-yl)pyrimidin-2-yl]amino}-4-methoxy-2-{4-methylpiperazin-1-yl}phenyl)prop-2-enamide収率 2%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 67153907CH2Cl2 2-methyltetrahydrofuran溶媒

反応条件

温度
2 °C

実験手順

To a stirred solution of N′-[4-(1H-indol-3-yl)pyrimidin-2-yl]-4-methoxy-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine (Intermediate 66, 96 mg, 0.22 mmol) in CH2Cl2 (15 mL) at 2° C. was added DIPEA (0.039 mL, 0.22 mmol) and acryloyl chloride (0.018 mL, 0.22 mmol). The resulting solution was stirred at 2° C. for 0.25 h, then allowed to warm to r.t. and stirred for a further 3.5 h. The mixture was then diluted with CH3OH (10 mL), loaded directly onto silica. Purification by FCC, eluting with 0-10% CH3OH in CH2Cl2 (containing 1% concentrated ammonia (aq) gave the an off-white solid which appeared to contain DIPEA.HCl according to MNR analysis. The solid was then dissolved in a 1:1 mixture of CH2Cl2/2-methyltetrahydrofuran (30 mL) and the resulting solution was washed with NaOH solution (2M, 2×30 mL), water (2×30 mL) and then sat. brine (30 mL). The organic solution was dried (MgSO4) and concentrated in vacuo to give the title compound (2 mg, 2%) as a white solid after trituration with diethyl ether. The liquors from the trituration were concentrated in vacuo to give a second sample of the title compound (10 mg, 9%) as a white solid; 1H NMR: 2.27 (3H, s), 2.55 (4H, s), 2.82-2.95 (4H, m), 3.84 (3H, d), 5.73 (1H, d), 6.24 (1H, dd), 6.62 (1H, dd), 6.89 (1H, s), 7.07-7.21 (2H, m), 7.25 (1H, d), 7.46 (1H, d), 7.89 (1H, s), 8.29 (1H, d), 8.32 (1H, d), 8.42 (1H, s), 8.69 (1H, s), 9.01 (1H, s); m/z: ES+ MH+ 484.62.

後処理

  1. temperatureto warm to r.t.
  2. stirringstirred for a further 3.5 h
  3. customPurification by FCC
  4. washeluting with 0-10% CH3OH in CH2Cl2 (
  5. additioncontaining 1% concentrated ammonia (aq)
  6. customgave the an off-white solid which
  7. washthe resulting solution was washed with NaOH solution (2M, 2×30 mL), water (2×30 mL)
  8. dry with materialThe organic solution was dried (MgSO4)
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-bb5c9a9bc1b149708ac177db73df3b22
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

反応ノート

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