Sodium Carbonate → 5-(8,8-Dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluoren-3-yl)-pyrimidin-2-ylamine

HRID 334179ノート

反応式

HRID 334179 の反応式
Cl[C:2]1[N:3]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:5]2[CH:6]=[C:7]3[N:12]([C:13]=2[N:14]=1)[CH2:11][CH2:10][O:9][C:8]3([CH3:16])[CH3:15].CC1(C)C(C)(C)OB([C:31]2[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:15][C:8]1([CH3:16])[C:7]2[N:12]([C:13]3[N:14]=[C:2]([C:31]4[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=4)[N:3]=[C:4]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:5]=3[CH:6]=2)[CH2:11][CH2:10][O:9]1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 866673893-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene

生成物 1

HCID 573839575-(8,8-Dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluoren-3-yl)-pyrimidin-2-ylamine収率 15%

試薬・触媒・溶媒 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)触媒HCID 6342Acetonitrile溶媒

反応条件

温度
150 °C

実験手順

A mixture of 3-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene (75 mg, 0.23 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (115 mg, 0.52 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)-phosphine)dichloropalladium(II) (25 mg, 0.035 mmol) and sodium carbonate (1 mL, 1.0 mmol, 1M aqueous solution) in acetonitrile (3 mL) was degassed and heated at 150° C. for 30 mins in a microwave reactor, then concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, gradient 0 to 75% ethyl acetate in cyclohexane) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient acetonitrile 5-98%) affording 177 as a off-white solid (13 mg, 15%). LCMS (method B): RT=3.50 min, [M+H]+=382. 1H NMR (400 MHz, CDCl3): δ 9.27 (2H, s), 6.12 (1H, s), 5.27 (2H, broad s), 4.21 (2H, m), 4.14 m), 3.88 (4H, m), 1.62 (6H, s)

後処理

  1. customwas degassed
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified by column chromatography (SiO2, gradient 0 to 75% ethyl acetate in cyclohexane)

出典と根拠

ORDレコード
ord-92f27845235e4feab6196c8d4a73a22d
出典データセット
uspto-grants-2014_11
特許番号
US08883799B2

反応ノート

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