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Sodium Carbonate → 5-(7-Methyl-4-morpholino-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)pyrimidin-2-amine

HRID 528461
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HRID 528461 반응식
Cl[C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[O:11][CH2:10][CH:9]([CH3:12])[O:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[N:29][C:30]([NH2:33])=[N:31][CH:32]=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][CH:9]1[O:8][C:6]2[N:7]=[C:2]([C:27]3[CH:28]=[N:29][C:30]([NH2:33])=[N:31][CH:32]=3)[N:3]=[C:4]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[C:5]=2[O:11][CH2:10]1
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참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 867117462-Chloro-7-methyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

생성물 1

HCID 734270385-(7-Methyl-4-morpholino-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)pyrimidin-2-amine

시약·촉매·용매 2

HCID 178418476
HCID 178418476, 화합물
촉매
HCID 6342Acetonitrile용매

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온도
140 °C

실험 절차

A mixture of 2-chloro-7-methyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine (99 mg, 0.36 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (97 mg, 0.44 mmol), Pd(PPh3)2Cl2 (28 mg, 0.04 mmol) and sodium carbonate (1.2 mL, 1.20 mmol, 1M aqueous solution) in acetonitrile (1.2 mL) was degassed then heated at 140° C. for 25 minutes using microwave irradiation. The reaction mixture was filtered, flushing with ethyl acetate. The filtrate phases were separated and the aqueous layer extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, gradient 0-4% methanol in DCM) then triturated with diethyl ether affording 103 as a white solid (12 mg, 11%). LCMS: RT=3.06 min, [M+H]+=331. 1H NMR (400 MHz, DMSO): δ 8.90 (2H, s), 7.01 (2H, s), 4.57-4.47 (1H, m), 4.36 (1H, dd, J=11.41, 2.34 Hz), 3.82 (1H, dd, J=11.43, 7.60 Hz), 3.77-3.61 (8H, m), 1.34 (3H, d, J=6.44 Hz)

후처리

  1. customwas degassed
  2. custommicrowave irradiation
  3. filtrationThe reaction mixture was filtered
  4. customflushing with ethyl acetate
  5. customThe filtrate phases were separated
  6. extractionthe aqueous layer extracted with ethyl acetate
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by column chromatography (SiO2, gradient 0-4% methanol in DCM)
  10. customthen triturated with diethyl ether affording 103 as a white solid (12 mg, 11%)

출처 및 근거

ORD 기록
ord-687a77488b554046a93fce80f8611219
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09346817B2

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