2-Benzimidazolepropanol → 2-[3-(1H-benzimidazol-2-yl)propoxy]-6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methylpyrimidin-4-amine

HRID 1626364ノート

反応式

HRID 1626364 の反応式
[Cl:1][C:2]1[N:7]=[C:6](S(C)(=O)=O)[N:5]=[C:4]([NH:12][CH2:13][C:14]2[S:18][C:17]([CH3:19])=[N:16][C:15]=2[CH3:20])[C:3]=1[CH3:21].[NH:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[CH2:31][CH2:32][CH2:33][OH:34].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[NH:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[CH2:31][CH2:32][CH2:33][O:34][C:6]1[N:5]=[C:4]([NH:12][CH2:13][C:14]2[S:18][C:17]([CH3:19])=[N:16][C:15]=2[CH3:20])[C:3]([CH3:21])=[C:2]([Cl:1])[N:7]=1

参加物

5

反応物 3

HCID 754702-BenzimidazolepropanolHCID 2724254Sodium bis(trimethylsilyl)amideHCID 86688161HCID 86688161、化合物

生成物 1

HCID 569494492-[3-(1H-benzimidazol-2-yl)propoxy]-6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methylpyrimidin-4-amine収率 82%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-methylsulfonyl-pyrimidin-4-amine F5 (480 mg, 1.384 mmol) and 3-(1H-benzimidazol-2-yl)propan-1-ol (244 mg, 1.38 mmol) were placed in a 20 mL vial and dissolved in THF (5 mL). A 1 M solution of NaHMDS in THF (1.38 mL, 1.38 mmol) was added, and the reaction was stirred overnight. Solvent was then removed, and the product was purified by silica gel flash column chromatography (EtOAc/hexanes gradient). 500 mg (82%) of F6 were isolated as an off-white foam. 1H NMR δ (300 MHz, DMSO-d6): 7.84-7.80 (1H, m), 7.76 (2H, dd, J=6.20, 3.18 Hz), 7.51 (2H, dd, J=6.28, 3.15 Hz), 4.46 (2H, d, J=5.76 Hz), 4.37-4.31 (2H, m), 2.54 (4H, s), 2.46 (3H, s), 2.29 (3H, s), 1.99 (3H, s). HRMS (Electrospray): m/z 443.1413 (MH+).

後処理

  1. customSolvent was then removed
  2. customthe product was purified by silica gel flash column chromatography (EtOAc/hexanes gradient)

出典と根拠

ORDレコード
ord-6c502a3edabd4e73a4fcff19328b72c2
出典データセット
uspto-grants-2014_07
特許番号
US08785467B2

反応ノート

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