Bromotrimethylsilane → [2-(4-{4-[4-Methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylcarbamoyl]-benzyl}-piperazin-1-yl)-ethyl]-phosphonic acid

HRID 2220142

反応式

HRID 2220142 の反応式
C([O:3][P:4]([CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24](=[O:46])[NH:25][C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[C:28]([NH:33][C:34]4[N:39]=[C:38]([C:40]5[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=5)[CH:37]=[CH:36][N:35]=4)[CH:27]=3)=[CH:20][CH:19]=2)[CH2:13][CH2:12]1)(=[O:8])[O:5]CC)C.C[Si](Br)(C)C>CN(C=O)C>[CH3:32][C:29]1[CH:30]=[CH:31][C:26]([NH:25][C:24]([C:21]2[CH:20]=[CH:19][C:18]([CH2:17][N:14]3[CH2:13][CH2:12][N:11]([CH2:10][CH2:9][P:4](=[O:3])([OH:5])[OH:8])[CH2:16][CH2:15]3)=[CH:23][CH:22]=2)=[O:46])=[CH:27][C:28]=1[NH:33][C:34]1[N:39]=[C:38]([C:40]2[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=2)[CH:37]=[CH:36][N:35]=1

参加物

4

反応物 2

HCID 76113Bromotrimethylsilane2 回HCID 59772964[2-(4-{4-[4-Methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylcarbamoyl]-benzyl}-piperazin-1-yl)-ethyl]-phosphonic acid diethyl ester

生成物 1

HCID 9873184[2-(4-{4-[4-Methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylcarbamoyl]-benzyl}-piperazin-1-yl)-ethyl]-phosphonic acid収率 59.6%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
110 °C

実験手順

To a solution of [2-(4-{4-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylcarbamoyl]-benzyl}-piperazin-1-yl)-ethyl]-phosphonic acid diethyl ester (8 mg, 0.012 mmol) in DMF (1 mL) was added TMSBr (15 μL, 0.12 mmol) at room temperature. The reaction was allowed to proceed at room temperature for 14 hours. Another portion of TMSBr (20 μL) was added and heated at 110° C. for 12 hours when completion of the reaction was detected by LCMS. The reaction was cooled down to room temperature and quenched with addition of MeOH. The reaction mixture was dried under reduced pressure and the residue was purified by RP HPLC using a C18 column with a gradient of H2O— Acetonitrile (5-100%) over 20 minutes to provide 4.2 mg (50%) of the product as mono-TFA salt. 1H NMR (300 MHz, CD3OD) δ 1.80-1.84 (m, 2H), 2.08-2.02 (m, 2H), 2.23 (s, 3H), 3.07 (bs, 4H), 3.30-3.32 (2H, possible overlap with solvent), 3.89 (m, 2H), 4.01 (s, 2H), 6.87 (s, 1H), 7.23-7.3 (m, 3H), 7.52-7.60 (m, 3H), 8.01 (d, 2H, J=8 Hz), 8.08 (dd, 1H, J=2, 5 Hz), 8.30 (s, 1H), 8.58 (d, 1H, J=5 Hz), 8.89 (d, 1H, J=2 Hz), 9.22 (dd, 1H, J=2, 5 Hz), 9.63 (s, 1H); 31P (121.4 MHz, CD3OD) δ 21.9; MS (m/z) 588 [M+H]+.

後処理

  1. temperatureThe reaction was cooled down to room temperature
  2. customquenched with addition of MeOH
  3. customThe reaction mixture was dried under reduced pressure
  4. customthe residue was purified by RP HPLC
  5. customover 20 minutes

出典と根拠

ORDレコード
ord-3e2ee45ef2de4d91ade8f66b89f10ef9
出典データセット
uspto-grants-2008_08
特許番号
US07417055B2

関連ノート

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