Sodium Carbonate → Butyl 4-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-6-[(methylsulfonyl)(propyl)amino]pyridine-2-carboxylate

HRID 899449ノート

反応式

HRID 899449 の反応式
[CH2:1]([C:8]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:27])[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[C:16]([N:18]([S:22]([CH3:25])(=[O:24])=[O:23])[CH2:19][CH2:20][CH3:21])[N:15]=[C:14](Cl)[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:36](=[O:39])([O-])[O-:37].[Na+].[Na+]>C(O)CCC.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl>[C:31]([O:30][C:29]([NH:28][C:8]([CH3:27])([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[C:16]([N:18]([S:22]([CH3:25])(=[O:24])=[O:23])[CH2:19][CH2:20][CH3:21])[N:15]=[C:14]([C:36]([O:37][CH2:8][CH2:1][CH2:2][CH3:3])=[O:39])[CH:13]=1)=[O:35])([CH3:34])([CH3:33])[CH3:32]

参加物

5

反応物 2

HCID 10340Sodium CarbonateHCID 58856338Tert-butyl [1-benzyl-2-({2-chloro-6-[(methylsulfonyl)(propyl)amino]pyridin-4-yl}methoxy)-1-methylethyl]carbamate2 回

生成物 1

HCID 67318238Butyl 4-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-6-[(methylsulfonyl)(propyl)amino]pyridine-2-carboxylate

試薬・触媒・溶媒 2

HCID 498840Bis(benzonitrile)palladium chloride触媒HCID 2631-Butanol溶媒

反応条件

温度
100 °C

実験手順

A suspension of tert-butyl [1-benzyl-2-({2-chloro-6-[(methylsulfonyl)(propyl)amino]pyridin-4-yl}methoxy)-1-methylethyl]carbamate (115 mg, 0.22 mmol, intermediate VI), sodium carbonate (70 mg, 0.66 mmol), PdCl2(PhCN)2 (2 mg, 0.004 mmol), 4A sieves and 1-[2-(dicyclohexylphasphanyl)ferrocenyl]ethyldicyclohexylphosphane (11 mg, 0.017 mmol, STREM) in n-butanol (2 ml, degassed with Argon), was purged with CO and stirred at 100° C. for 16 h under 1 atm of CO. The reaction mixture was diluted with dichloromethane, washed with water and brine, dried over sodium sulfate, concentrated in vacuo, azeothroped with toluene, and purified by flash chromatography (silica, 0-35% EtOAc/hexanes) to provide butyl 4-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-6-[(methylsulfonyl)(propyl)amino]pyridine-2-carboxylate as a yellow oil which was dissolved in 1:1 THF:MeOH (1.6 mL) and treated with aq LiOH (0.38 mL, 0.38 mmol, 1N) for 2 h at rt. The reaction mixture was acidified to pH 3-4 with 1N HCl, extracted with dichloromethane, dried over sodium sulfate, concentrated in vacuo, azeothroped with toluene to give 4-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-6-[(methylsulfonyl)(propyl)amino]pyridine-2-carboxylic acid as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.71 (s, 1H), 7.34-7.13 (m, 5H), 4.67 (s, 2H), 4.49 (s, 1H), 3.93 (t, J=7.6 Hz, 2H), 3.72 (A of AB, d, J=9.2 Hz, 1H), 3.62 (B of AB, d, J=9.2 Hz, 1H), 3.17 (A of AB, d, J=13.6 Hz, 1H), 3.05 (s, 3H), 2.90 (13 of AB, d, J=13.6 Hz, 1H), 1.70-1.55 (m, 2H), 1.46 (s, 9H), 1.27 (s, 3H), 0.96 (t, J=7.6 Hz, 3H).

後処理

  1. customwas purged with CO
  2. additionThe reaction mixture was diluted with dichloromethane
  3. washwashed with water and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. custompurified by flash chromatography (silica, 0-35% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-f8ba6a0da2fe4c0789a74a61cff46bb2
出典データセット
uspto-grants-2008_04
特許番号
US07354942B2

反応ノート

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