Morpholine → 4,4'-(6-Chloropyrimidine-2,4-diyl)dimorpholine

HRID 1512142

반응식

HRID 1512142 반응식
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[C:11]([Cl:13])[CH:10]=[C:9](Cl)[N:8]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.CCOC(C)=O>CN1C(=O)CCC1>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[N:8]=[C:9]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:10]=[C:11]([Cl:13])[N:12]=2)[CH2:5][CH2:6]1

참가 물질

6

반응물 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 27720684-(4,6-Dichloropyrimidin-2-yl)morpholine

생성물 1

HCID 6863344,4'-(6-Chloropyrimidine-2,4-diyl)dimorpholine수율 93%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
85 °C

실험 절차

To a slurry of 2-morpholino-4,6-dichloropyrimidine (prepared as in Method 22, 2.0 g, 8.54 mmol) in NMP (14 mL), triethylamine (1.43 mL, 10.25 mmol) was added. The heterogeneous mixture was stirred for 15 minutes, then treated with morpholine (0.75 mL, 8.54 mmol). Upon refluxing at 85° C. under argon for 2 hours, the solution was cooled, then added to EtOAc (160 mL). The organic solution was washed with 25 mL of NaHCO3(sat.) (2×), water (2×) and brine, dried over Na2SO4, filtered and concentrated. The crude material was dissolved in 200 mL EtOAc and filtered through a SiO2 pad, further eluting with EtOAc, yielding 2.2 g (93%) of 2,4-dimorpholino-6-chloropyrimidine as an off-white solid. LCMS (m/z): 285.0 (MH+), 1H NMR (CDCl3): δ 5.86 (s, 1H), 3.71-3.76 (m, 12H), 3.52-3.56 (m, 4H).

후처리

  1. temperaturethe solution was cooled
  2. washThe organic solution was washed with 25 mL of NaHCO3(sat.) (2×), water (2×) and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude material was dissolved in 200 mL EtOAc
  7. filtrationfiltered through a SiO2 pad
  8. washfurther eluting with EtOAc

출처 및 근거

ORD 기록
ord-70a4ae61e28048b5951c14898a2de0d4
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217035B2

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