Triethylamine → HCID 86690359、化合物

HRID 575909ノート

反応式

HRID 575909 の反応式
[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

参加物

6

反応物 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

生成物 1

HCID 86690359HCID 86690359、化合物収率 92%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-399ba8a01b8b44d79eef8aa9ab05e2ad
出典データセット
uspto-grants-2015_05
特許番号
US09035053B2

反応ノート

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