Pivaloyl chloride → HCID 91192837, 화합물

HRID 397993노트

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HRID 397993 반응식
[CH2:1]([NH:9][C:10]1[N:18]=[C:17]([NH:19][CH2:20][CH2:21][C:22]2[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=2)[N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[C@H:28]1[C@@H:32]2[O:33]C(C)(C)[O:35][C@@H:31]2[C@@H:30]([C:38]([OH:40])=O)[O:29]1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.CC(C)(C)[C:52](Cl)=[O:53].O[NH:58][C:59](=[NH:62])[CH2:60][CH3:61].C(Cl)Cl.C1C[O:69][CH2:68]C1>FC(F)(F)C(O)=O.O>[CH:68]([O:33][C@@H:32]1[C@H:31]([O:35][CH:52]=[O:53])[C@@H:30]([C:38]2[O:40][N:62]=[C:59]([CH2:60][CH3:61])[N:58]=2)[O:29][C@H:28]1[N:14]1[CH:13]=[N:12][C:11]2[C:15]1=[N:16][C:17]([NH:19][CH2:20][CH2:21][C:22]1[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=1)=[N:18][C:10]=2[NH:9][CH2:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)=[O:69]

참가 물질

7

반응물 5

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 21919333Tetrahydrofurane dichloromethaneHCID 70021813HCID 70021813, 화합물HCID 178458070HCID 178458070, 화합물

생성물 1

HCID 91192837HCID 91192837, 화합물

시약·촉매·용매 1

HCID 22392675Trifluoroacetic acid water용매

실험 절차

Intermediate 34 (0.083 mg, 0.15 mmol) was dissolved in DCM/THF (9:1, 3 ml) using sonication by ultrasound. N,N-diisopropylethylamine (0.057 ml, 3.32 mmol) and trimethylacetyl chloride (0.021 ml, 0.16 mmol) were added at 0° C. with stirring under nitrogen. The reaction was allowed to warm to room temperature over 2 h, cooled again to 0° C. and N-hydroxy-propionamidine (0.015 g, 0.18 mmol in 0.5 ml tetrahydrofuran) added with stirring. The reaction was allowed to warm to room temperature and stirred for 16 h. The solvents were evaporated in vacuo and the reaction mixture dissolved in toluene (10 ml). The reaction was heated to reflux (120° C.) for 8 h. The product was purified on a Varian Mega Bond Elut cartridge (5 g Si, 20 ml size) eluting with ethyl acetate/methanol (50:1-1:1) to afford crude product as a yellow oil (0.01 g). The product dissolved in trifluoroacetic acid/water (4 ml, 9:1) at 0° C. with stirring under nitrogen for 4 h. The solvents were evaporated in vacuo, azeotroped with toluene (2×50 ml) and purification using Autoprep. HPLC afforded title compound as yellow gum (0.004 g) LCMS SYSTEM C Rt=2.39 min m/z=561 MH+

후처리

  1. customsonication by ultrasound
  2. temperaturecooled again to 0° C.
  3. stirringwith stirring
  4. temperatureto warm to room temperature
  5. stirringstirred for 16 h
  6. customThe solvents were evaporated in vacuo
  7. dissolutionthe reaction mixture dissolved in toluene (10 ml)
  8. temperatureThe reaction was heated
  9. temperatureto reflux (120° C.) for 8 h
  10. customThe product was purified on a Varian Mega Bond Elut cartridge (5 g Si, 20 ml size)
  11. washeluting with ethyl acetate/methanol (50:1-1:1)
  12. customto afford crude product as a yellow oil (0.01 g)
  13. stirringwith stirring under nitrogen for 4 h
  14. customThe solvents were evaporated in vacuo
  15. customazeotroped with toluene (2×50 ml) and purification

출처 및 근거

ORD 기록
ord-9897c69ee8f946ec83c949718f6abc9d
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06610665B1

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