Sodium Carbonate → 3-(7,7-dimethyl-4-morpholino-6H-[1,4]dioxino[2,3-d]pyrimidin-2-yl)phenol

HRID 528481

反応式

HRID 528481 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:11][CH2:10][C:9]([CH3:13])([CH3:12])[O:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[C:30]([OH:34])[CH:31]=[CH: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>[CH3:12][C:9]1([CH3:13])[O:8][C:6]2[N:7]=[C:2]([C:28]3[CH:29]=[C:30]([OH:34])[CH:31]=[CH:32][CH:33]=3)[N:3]=[C:4]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:5]=2[O:11][CH2:10]1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 27346233-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 867117472-Chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

生成物 1

HCID 734271383-(7,7-dimethyl-4-morpholino-6H-[1,4]dioxino[2,3-d]pyrimidin-2-yl)phenol

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 microwave vial was charged with 2-chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine from Example 104 (50 mg, 0.18 mmol), 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (58 mg, 0.26 mmol), Pd(PPh3)2Cl2 (12 mg, 0.02 mmol) and sodium carbonate (0.5 mL, 0.5 mmol, 1M aqueous solution) in acetonitrile (1.5 mL) then evacuated and back filled with nitrogen before being 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 trituration with diethyl ether affording 109 as a white solid (38 mg, 63%). LCMS: RT=4.13 min, [M+H]+=344. 1H NMR (400 MHz, CDCl3): δ 7.87-7.82 (2H, m), 7.26 (1H, t, J=7.6 Hz), 6.91 (1H, dd, J=2.4, 7.6 Hz), 3.92 (2H, s), 3.90-3.80 (8H, m), 1.47 (6H, s).

後処理

  1. customthen evacuated
  2. additionback filled with nitrogen
  3. custommicrowave irradiation
  4. washwas washed with methanol
  5. washthe product eluted with 2M ammonia in methanol
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by trituration with diethyl ether affording 109 as a white solid (38 mg, 63%)

出典と根拠

ORDレコード
ord-dc9ec2c02d91475788539cffd7d4ef2a
出典データセット
uspto-grants-2016_05
特許番号
US09346817B2

関連ノート

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