Hydrochloric Acid → HCID 178514784, 화합물

HRID 881143노트

반응식

HRID 881143 반응식
[Br:1][C:2]1[CH:3]=[C:4]([N:9]2C(=O)[O:12][N:11]=[C:10]2[C:15]2[C:16]([NH:20][CH2:21][CH2:22][NH:23][S:24]([NH2:27])(=[O:26])=[O:25])=[N:17][O:18][N:19]=2)[CH:5]=[CH:6][C:7]=1[F:8].FC(F)(F)C(O)=O.[OH-].[Na+].Cl>C1COCC1>[NH2:27][S:24]([NH:23][CH2:22][CH2:21][NH:20][C:16]1[C:15]([C:10](=[N:11][OH:12])[NH:9][C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Br:1])[CH:3]=2)=[N:19][O:18][N:17]=1)(=[O:25])=[O:26]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 66605130N-[2-({4-[4-(3-Bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]sulfamide

생성물 1

HCID 178514784HCID 178514784, 화합물수율 336.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a crude mixture of N-[2-({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]sulfamide (2.4 mol) containing residual amounts of trifluoroacetic acid stirring in a 22 L flask was added THF (5 L). The resulting solution was cooled to 0° C. using an ice bath and 2 N NaOH (4 L) was added at a rate so that the temperature did not exceed 10° C. After stirring at ambient temperature for 3 h (LCMS indicated no starting material remained), the pH was adjusted to 3-4 with concentrated HCl (˜500 mL). The THF was removed in vacuo, and the resulting mixture was extracted with ethyl acetate (15 L). The organic layer was washed with water (5 L), brine (5 L), and the solvents removed in vacuo to afford a solid. The solid was triturated with MTBE (2×2 L), combined with three other reactions of the same size, and dried overnight in a convection oven to afford a white solid (3535 g). The solid was recrystallized (3×22 L flasks, 2:1 water:ethanol, 14.1 L each flask) and dried in a 50° C. convection oven to a constant weight to furnish the title compound as an off-white solid (3290 g, 78%). LCMS for C11H14BrFN7O4S (M+H)+: m/z=437.9, 439.9. 1H NMR (400 MHz, DMSO-d6): δ 11.51 (s, 1H), 8.90 (s, 1H), 7.17 (t, J=8.8 Hz, 1H), 7.11 (dd, J=6.1, 2.7 Hz, 1H), 6.76 (m, 1H), 6.71 (t, J=6.0 Hz, 1H), 6.59 (s, 2H), 6.23 (t, J=6.1 Hz, 1H), 3.35 (dd, J=10.9, 7.0 Hz, 2H), 3.10 (dd, J=12.1, 6.2 Hz, 2H).

후처리

  1. customdid not exceed 10° C
  2. customThe THF was removed in vacuo
  3. extractionthe resulting mixture was extracted with ethyl acetate (15 L)
  4. washThe organic layer was washed with water (5 L), brine (5 L)
  5. customthe solvents removed in vacuo
  6. customto afford a solid
  7. customThe solid was triturated with MTBE (2×2 L)
  8. customdried overnight in a convection oven

출처 및 근거

ORD 기록
ord-f4c11b82c3e648be901faee0099d0324
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993605B2

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