Proton sponge → HCID 54583743, 화합물

HRID 2077034노트

반응식

HRID 2077034 반응식
CN(C)C1C2C(=CC=CC=2N(C)C)C=CC=1.C([N:24]1[CH2:30][CH2:29][C:28]2[CH:31]=[N:32][C:33]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=3)=[N:34][C:27]=2[CH2:26][CH2:25]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>ClCCl>[Cl:42][C:38]1[CH:37]=[C:36]([CH:41]=[CH:40][CH:39]=1)[CH2:35][C:33]1[N:32]=[CH:31][C:28]2[CH2:29][CH2:30][NH:24][CH2:25][CH2:26][C:27]=2[N:34]=1

참가 물질

5

반응물 3

HCID 88675Proton spongeHCID 5213051-Chloroethyl chloroformateHCID 59312283HCID 59312283, 화합물

생성물 1

HCID 54583743HCID 54583743, 화합물수율 18%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

1,8-Bis-(dimethylamino)naphthalene (80 mg, 0.37 mmol) was added to a solution of 7-benzyl-2-(3-chlorobenzyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine of Preparation 28, Step C, (135 mg, 0.37 mmol) in dichloromethane (5 ml). Then 1-chloroethyl chloroformate (80.9 μl, 0.74 mmol) was added and stirred at room temperature for 16 h. The reaction mixture was diluted with dichloromethane (10 ml) then washed with 5% aqueous citric acid (15 ml). The organic phase was dried over magnesium sulphate and concentrated in vacuo. The residue was dissolved in methanol (5 ml) then heated to reflux, under nitrogen, for 1.5 h. The reaction mixture was concentrated in vacuo then the residue was partitioned between dichloromethane (10 ml) and 1N NaOH (10 ml). The organic phase was dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with DCM:MeOH:0.880NH3 (100:0:0 to 90:10:1), to afford the title compound as a yellow oil in 18% yield, 18 mg.

후처리

  1. washthen washed with 5% aqueous citric acid (15 ml)
  2. dry with materialThe organic phase was dried over magnesium sulphate
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in methanol (5 ml)
  5. temperaturethen heated
  6. temperatureto reflux, under nitrogen, for 1.5 h
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. customthe residue was partitioned between dichloromethane (10 ml) and 1N NaOH (10 ml)
  9. dry with materialThe organic phase was dried over magnesium sulphate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography on silica gel
  12. washeluting with DCM

출처 및 근거

ORD 기록
ord-0dd13a66c7f4464d8b7e6c414a627724
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07928099B2

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