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

HRID 528481

반응식

HRID 528481 반응식
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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 6342Acetonitrile용매

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온도
120 °C

실험 절차

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).

후처리

  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%)

출처 및 근거

ORD 기록
ord-dc9ec2c02d91475788539cffd7d4ef2a
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346817B2

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