Sodium Carbonate → 2-(2-aminopyrimidin-5-yl)-8-methyl-4-morpholino-6H-pyrimido[5,4-b][1,4]oxazin-7(8H)-one

HRID 528500ノート

反応式

HRID 528500 の反応式
Cl[C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[O:6][CH2:7][C:8](=[O:13])[N:9]([CH3:12])[C:10]=2[N:11]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[N:30][C:31]([NH2:34])=[N:32][CH:33]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:34][C:31]1[N:32]=[CH:33][C:28]([C:2]2[N:3]=[C:4]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:5]3[O:6][CH2:7][C:8](=[O:13])[N:9]([CH3:12])[C:10]=3[N:11]=2)=[CH:29][N:30]=1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 867117722-Chloro-8-methyl-4-morpholin-4-yl-8H-pyrimido[5,4-b][1,4]oxazin-7-one

生成物 1

HCID 867117732-(2-aminopyrimidin-5-yl)-8-methyl-4-morpholino-6H-pyrimido[5,4-b][1,4]oxazin-7(8H)-one収率 71.6%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 6342Acetonitrile溶媒

反応条件

温度
120 °C

実験手順

A mixture of 2-chloro-8-methyl-4-morpholin-4-yl-8H-pyrimido[5,4-b][1,4]oxazin-7-one (100 mg, 0.35 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (116 mg, 0.53 mmol), Pd(PPh3)2Cl2 (25 mg, 0.035 mmol) and sodium carbonate (1.0 mL, 1.0 mmol, 1M aqueous solution) in acetonitrile (4 mL) was degassed then heated at 120° C. for 30 minutes using microwave irradiation. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with methanol and the product eluted with 2M ammonia in methanol. The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient of acetonitrile 5-98%) affording 120 as a white solid (86 mg, 71%). LCMS: RT=3.04 min, [M+H]+=344. 1H NMR (400 MHz, CDCl3): δ 9.14 (2H, s), 5.25 (2H, broad s), 4.62 (2H, s), 3.81 (8H, s), 3.49 (3H, s).

後処理

  1. customwas degassed
  2. custommicrowave irradiation
  3. washwas washed with methanol
  4. washthe product eluted with 2M ammonia in methanol
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient of acetonitrile 5-98%)

出典と根拠

ORDレコード
ord-533e8bb4122a46898e1a937555aac64b
出典データセット
uspto-grants-2016_05
特許番号
US09346817B2

反応ノート

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