Triethylamine → HCID 86690359, 화합물

HRID 575909노트

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HRID 575909 반응식
[Br:1][C:2]1[N:3]=[C:4]([C:23]#[CH:24])[C:5]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:6][CH:7]=1.Cl[C:26](=[N:48][OH:49])[C:27]1[CH:47]=[CH:46][C:30]([CH2:31][N:32]([CH:40]2CCOCC2)[C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:29][CH:28]=1.C(N(CC)CC)C>C(Cl)Cl.O>[Br:1][C:2]1[N:3]=[C:4]([C:23]2[O:49][N:48]=[C:26]([C:27]3[CH:28]=[CH:29][C:30]([CH2:31][N:32]([C:33]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:39])[CH3:40])=[CH:46][CH:47]=3)[CH:24]=2)[C:5]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9](=[O:15])[O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[N:6][CH:7]=1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 58070394tert-butyl N-(5-bromo-3-ethynylpyrazin-2-yl)-N-[(tert-butoxy)carbonyl]carbamateHCID 86680728tert-butyl 4-(chloro(hydroxyimino)methyl)benzyl(tetrahydro-2H-pyran-4-yl)carbamate

생성물 1

HCID 86690359HCID 86690359, 화합물수율 92%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

A suspension of tert-butyl N-(5-bromo-3-ethynylpyrazin-2-yl)-N-tert-butoxycarbonylcarbamate (Compound 4-iii) (1.59 kg, 3.99 mol) and tert-butyl 4-(chloro(hydroxyimino)methyl)benzyl(tetrahydro-2H-pyran-4-yl)carbamate (1.31 kg, 4.39 mol; 1.10 equiv.) in CH2Cl2 (12.7 L) is stirred at ambient temperature. Triethylamine (444 g, 611 mL, 4.39 mol) is added to the suspension and the reaction temperature is maintained between 20-30° C. for 20-48 h to ensure complete reaction. The reaction mixture is diluted with water (8 L) and thoroughly mixed, then the phases are separated. The organic phase is washed with water (8 L), dried (Na2SO4), and then concentrated until about 1 L of CH2Cl2 remains. The concentrate is diluted with heptane (3.2 L) and re-concentrated at 40° C./200 torr until no distillate is observed. The concentrate is stirred and further diluted with heptane (12.7 L) to precipitate a solid. The suspension is stirred overnight. The solid is collected by filtration, washed with heptane (2×3 L) then dried to afford Compound 4-iv (2.42 kg; 92% yield, 100 area % purity by HPLC) as a light tan powder. 1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 7.82 (d, J=8.2 Hz, 2H), 7.31 (m, 3H), 4.46 (br s, 2H), 2.84 (br d, 3H), 1.57 (s, 2H), 1.44 (br s, 9H), 1.36 (s, 18H).

후처리

  1. temperaturethe reaction temperature is maintained between 20-30° C. for 20-48 h
  2. customreaction
  3. additionthoroughly mixed
  4. customthe phases are separated
  5. washThe organic phase is washed with water (8 L)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated until about 1 L of CH2Cl2
  8. additionThe concentrate is diluted with heptane (3.2 L)
  9. concentrationre-concentrated at 40° C./200 torr until no distillate
  10. stirringThe concentrate is stirred
  11. additionfurther diluted with heptane (12.7 L)
  12. customto precipitate a solid
  13. stirringThe suspension is stirred overnight
  14. filtrationThe solid is collected by filtration
  15. washwashed with heptane (2×3 L)
  16. customthen dried
  17. customto afford Compound 4-iv (2.42 kg; 92% yield, 100 area % purity by HPLC) as a light tan powder

출처 및 근거

ORD 기록
ord-399ba8a01b8b44d79eef8aa9ab05e2ad
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09035053B2

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