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

HRID 1512142

反応式

HRID 1512142 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
85 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-70a4ae61e28048b5951c14898a2de0d4
出典データセット
uspto-grants-2012_07
特許番号
US08217035B2

関連ノート

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